Pancreas

pancreas for MBBS, undergraduate sudents

1. PANCREAS DR. Prajwal R K DEPARTMENT OF GENERAL SURGERY KEMPEGOWDA INSTITUTE OF MEDICAL SCIENCES, BANGALORE

2. ANATOMY Pancreas – Greek ‘pan’ (all) and ‘ kreas ’ (flesh) Divided into Head(30%), Body and tail(70%). 80–90% is composed of exocrine acinar tissue Weight – approximately 80 grams

3. ANATOMY

4. Anatomic Relations The head lies within the curve of the duodenum the body of the second lumbar vertebra and the vena cava. The aorta and the superior mesenteric vessels lie behind the neck of the gland.

5. Anatomic Relations Coming off the side of the pancreatic head is the uncinate process Which lies behind the superior mesenteric vein. The tip of the pancreatic tail extends up to the splenic hilum.

6. Anatomic Relations

7. Exocrine PANCREAS 80–90% OF PANCREAS (exocrine acinar tissue) organized into lobules The main pancreatic duct branches into interlobular and intralobular ducts, ductules and, finally, acini. The main duct is lined by columnar epithelium, cuboidal in the ductules .

8. Exocrine PANCREAS

9. Exocrine PANCREAS

10. endocrine pancreas Clusters of endocrine cells, known as islets of Langerhans 75% are B cells (producing insulin); 20% are A cells (producing glucagon); D cells (producing somatostatin) F cells (pancreatic polypeptide) B cells form an inner core the islet cells Splenic drain into the portal vein

11. endocrine pancreas

12. DEVELOPMENT OF PANCREAS Day 26 – Dorsal pancreatic duct arises from the dorsal side of the duodenum Day 32 – Ventral bud arises from the base of the hepatic diverticulum

13. DEVELOPMENT OF PANCREAS Day 37 - Contact occurs between the two buds. Fusion by the end of week 6

14. DEVELOPMENT OF PANCREAS Week 6 Ventral bud produces the head and uncinate process Ducts fuse Ventral duct and distal portion of the dorsal duct form the main duct ( duct of Wirsung ) Proximal dorsal duct forms the duct of Santorini

15. DEVELOPMENT OF PANCREAS Month 3 – Acini appear Months 3–4 – Islets of Langerhans appear and become biologically active

16. DEVELOPMENT OF PANCREAS

17. DEVELOPMENT OF PANCREAS

18. arterial supply of the pancreas Anterior and posterior superior pancreatoduodenal artery Branch of Gastro duodenal artery Anterior and posterior inferior pancreatoduodenal artery Branch of superior mesenteric artery. Inferior pancreatic artery Superior pancreatic artery Splenic and left gastroepiploic artery

19. arterial supply of the pancreas

20. arterial supply of the pancreas

21. VENOUS DRINAGE of the pancreas

22. DUCTAL SYSTEM OF PANCREAS Duct of Wirsung (MPD) – empties into the ampulla of Vater together with the CBD. Duct of Santorini – drains into the minor papilla approximately 2 cm above and medial to the ampulla of Vater (minor ductal system)

23. DUCTAL SYSTEM OF PANCREAS

24. Variations in the pancreatic ducts ‘Normal’ pancreatic ducts 60%

25. Variations in the pancreatic ducts Suppression of the accessory duct (Santorini) – 30% Accessory duct does not open into the Minor duodenal papilla Accessory duct does not communicate with the main pancreatic duct

26. Variations in the pancreatic ducts Suppression of the accessory duct (Santorini) – 30% Accessory duct ABSENT

27. Variations in the pancreatic ducts Suppression of the main duct ( Wirsung ) – 10% Accessory duct does not communicate with the main pancreatic duct Open separately into the duodenum at major and minor duodenal papilla- this leads to pancreas divisum

28. Variations in the pancreatic ducts Suppression of the main duct ( Wirsung ) – 10% Main pancreatic duct duct absent

29. sphincter of Oddi The outlet of each duct is protected by a complex sphincter mechanism Superior choledochal sphincter inferior choledochal sphincter ampullary sphincter pancreatic sphincter

30. Variations in the ampulla of Vater there is a common channel with no sphincter mechanism protecting flow between the ducts Gallstone pancreatitis is more likely

31. Variations in the ampulla of Vater there is a partial common channel Gallstone pancreatitis is more likely

32. Variations in the ampulla of Vater there is separation of the two channels

33. Anomalies of the pancreas Aplasia Hypoplasia Hyperplasia Hypertrophy Dysplasia Ectopic pancreatic tissue Accessory pancreas Vascular anomalies Choledochal cysts Horseshoe pancreas Variations and anomalies of the ducts Pancreas divisum Rotational anomalies Annular pancreas Pancreatic gall bladder Polycystic disease Congenital pancreatic cysts Cystic fibrosis Von Hippel–Lindau syndrome

34. CONGENITAL ANAMOLIES OF PANCREAS ANNULAR PANCREAS Failure of complete rotation of the ventral pancreatic bud a ring of pancreatic tissue surrounds the second or third part of the duodenum. Associated with congenital duodenal stenosis or atresia Most commonly seen in Down’s syndrome. Presents with Duodenal Obstruction Treatment is bypass ( duodenoduodenostomy ).

35. CONGENITAL ANAMOLIES OF PANCREAS

36. CONGENITAL ANAMOLIES OF PANCREAS PANCREAS DIVISUM Most common congenital pancreatic ductal anatomical variant Dominant dorsal duct which drains through the minor papilla Failure of fusion of dorsal and ventral pancreatic duct

37. CONGENITAL ANAMOLIES OF PANCREAS Classic pancreatic divisum anatomy Small ventral duct drains through major papilla Large dorsal duct draining through the minor papilla No communication between the ventral and dorsal ducts

38. CONGENITAL ANAMOLIES OF PANCREAS

39. CONGENITAL ANAMOLIES OF PANCREAS CLINICAL FEATURES: Asymptomatic 4-14% detected at autopsy series 3-8% at ERCP 9% at MRCP Recurrent acute pancreatitis, chronic pancreatitis Minor papilla - incomplete drainage. One of the congenital causes for recurrent pancreatitis IMAGING: MRCP EUS ERCP

40. CONGENITAL ANAMOLIES OF PANCREAS MRCP: (a) gall bladder, (b) bile duct crossing the (c) long duct of Santorini , (d) a short pancreatic duct together with the bile duct on the major duodenal papilla, (e) imaged with renal collecting system

41. CONGENITAL ANAMOLIES OF PANCREAS TREATMENT: Endoscopic sphincterotomy and stenting of the minor papilla may relieve the symptoms. Surgical intervention Sphincteroplasty, Pancreatojejunostomy Resection of the pancreatic head.

42. Physiology of the secretion of pancreatic enzymes 2 Major Functions – Exocrine and Endocrine Exocrine Pancreas The pancreas secretes approximately 500 to 800 mL per day colorless, odorless, alkaline (pH-8.4) , isosmotic pancreatic juice. Pancreatic juice is a combination of acinar cell and duct cell secretions.

43. Physiology of the secretion of pancreatic enzymes

44. Physiology of the secretion of pancreatic enzymes The proteolytic enzymes are secreted as proenzymes that require activation. Trypsinogen activation within the pancreas is prevented by the presence of inhibitors that are also secreted by the acinar cells. A failure to express a normal trypsinogen inhibitor, pancreatic secretory trypsin inhibitor (PSTI), also known as serine protease inhibitor Kazal type 1 (SPINK1), is a cause of familial pancreatitis

45. Physiology of the secretion of pancreatic enzymes

46. Physiology of the secretion of pancreatic enzymes The presence of peptides and fatty acids from food triggers the release of cholecystokinin (CCK). CCK induces the release of pancreatic enzymes into the duodenal lumen. S cells located in the duodenum release secretin in response to the acidification of the duodenum. Secretin induces the secretion of HCO3 − from pancreatic cells into the duodenum.

47. Physiology of the secretion of pancreatic enzymes Endocrine Pancreas

48. Investigation of the pancreas Serum enzyme levels Pancreatic function tests Morphology Ultrasound scan Computed tomography Magnetic resonance imaging Endoscopic retrograde cholangiopancreatography Endoscopic ultrasound Plain radiography Chest Upper abdomen

49. Investigation of the pancreas Measurement of Serum Amylase levels can identify pancreatic pathology as serum amylase raises in conditions like Acute pancreatitis. The serum amylase rises within a few hours of pancreatic damage and declines over the next 4-8 days SENSITIVE BUT NOT SPECIFIC

50. 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

51. Other Lab Investigations Urine Amylase Amylase : Creatinine Ratio Serum Lipase- MORE SPECIFIC THAN SERUM AMYLASE , Raises early and lasts for long PANCRETIC FUNCTION TESTS LUNDH TEST- Oral Meal Ingestion IV SECRETIN TEST NBT PABA TEST STOOL ELASTASE Duodenal intubation and measurement of amount of secretion

52. Pancreatic exocrine function can be assessed by directly measuring pancreatic secretion in response to a standardised stimulus – followed by duodenal intubation and measurement of amount of secretion The stimulus to secretion can be A) physiological, e.g. ingestion of a test meal, as in the Lundh test B) pharmacological, e.g. intravenous injection of a hormone, such as secretin or CCK.

53. NBT PABA TEST-- Nitroblue tetrazolium –para- aminobenzoic acid (NBT–PABA) Indirect measure of pancreatic function NBT–PABA is administered orally and degraded by pancreatic enzyme, and the breakdown product (PABA) is absorbed and excreted in the urine Urinary PABA levels is measured Pancreolauryl test- same principle as above- Fluorescein dilaurate Urinary flurosscein levels estimated STOOL ELASTASE – elastase levels in the stool is measured

54. RADIOLOGICAL INVESTIGATIONS XRAY ABDOMEN COLON CUT OFF SIGN – Acute Pancreatitis - CALCIFICATIONS- Chronic Pancreatitis

55. Abrupt cut off of colonic gas coloumn at splenic flexure- colon cutoff sign Colon beyond this point is decompressed by normal peristalsis

56. Abrupt cut off of colonic gas coloumn at splenic flexure- colon cutoff sign Colon beyond this point is decompressed by normal peristalsis

57. ULTRASONOGRAPHY Ultrasonography is the initial investigation of choice in patients with jaundice to determine bile duct is dilated or not and liver metastases present or absent Bulky Pancreas in Pancreatitis Vessel Thrombosis can be identified Can Detect mass in the pancreas Pseudocyst can be identified easily Obesity and overlying bowel gas are limiting Factors

58. CT ABDOMEN Pancreatic carcinomas of 1–2 cm in size can be identified Endocrine tumours are also well imaged In pancreatitis, necrotic areas within the gland can be identified by the absence of contrast enhancement on CT. Inflammatory collections and pseudocysts can be seen

59. CT-guided drainage is helpful in the treatment of pancreatic collections, cysts and pseudocysts Facilitates percutaneous fine-needle or Trucut biopsy Plus it is not operator dependent and bowel gas doesn’t affect imaging Current gold standard for imaging pancreas

60. The dilated bile duct (1) and main pancreatic duct (2) can be seen, with tumour infiltration around them. There is a thrombus in the superior mesenteric vein (3). The gall bladder is distended (4)  Carcinoma of Pancreatic head

61. MRI ABDOMEN Pancreas can be clearly identified, and clear images of the bile duct and the pancreatic duct, together with fluid collections, can be defined. Small tumors can be identified in the head/body of pancreas with greater accuracy than CT. Other structures like bile ducts and pancreatic ducts can also be identified.

62. MRCP Magnetic resonance cholangiography and pancreatography (MRCP) is a special sequence of MRI MRCP identifies Bile Ducts and obstruction beter than other modalities and gives information similar to ERCP without invasive procedures No contrast is needed

63. Using MRCP in conjunction with intravenous injection of secretin, emptying of the pancreatic duct can be demonstrated to show the absence or presence of obstruction.

64. ENDOSCOPIC RETROGRADE CHOLANGIOPANCREATOGRAPHY [ERCP] Both a diagnostic and therapeutic modality Using a side-viewing endoscope the ampulla of Vater can be identified and cannulated Injection of water-soluble contrast directly into the bile duct provides excellent images of the ductal anatomy

65. Reduced use for diagnostic purposes now – Endoscopic ultrasound and MRCP Widespread availability Cheaper Non invasive and less risky Currently mainly therapeutic ERCP still has a real role in the assessment of the patient with OBSTRUCTIVE JAUNDICE.

66. IRREGULAR STRICTURE OF PACREATIC DUCT- S/O Carcinoma

67. ENDOSCOPIC ULTRASOUND An ultrasound probe is attached to the tip of endoscope and visualization of diff layers of the duodenum and pancreas is possible Can asses: The location and depth of invasion of a tumour in pancreas Calculi in pancreatic duct Biopsy can also be taken under guidance Endoscopic drainage of pseudocyst

68. PANCREATITIS ‘Pancreatitis is inflammation of the pancreatic parenchyma’ Acute pancreatitis Recurrent pancreatitis Chronic pancreatitis

69. ACUTE PANCREATITIS Acute pancreatitis is defined as an acute condition presenting with abdominal pain, 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 Premature activation of pancreatic enzymes Autodigestion

70. ACUTE PANCREATITIS Under normal circumstances – pancreas protected from auto-digestion by following mechanisms: Most digestive enzymes are synthesized as inactive pro enzymes Most of these pro enzymes are activated by trypsin in the duodenum , intrapancreatic activation of the enzymes is minimal

71. ACUTE PANCREATITIS Typsinogen gets activated in the duodenum Acinar and ductal cells secretes trypsin inhibitors , which limits intrapancreatic trypsin activity

72. CLINICAL TYPES OF Acute PANCREATITIS mild ( interstitial oedematous pancreatitis ) interstitial oedema of the gland and minimal organ dysfunction. The majority (80%) will have mild attack of pancreatitis, the mortality around 1% severe ( necrotising pancreatitis ) seen in 5–10% of patients, pancreatic necrosis, a severe systemic inflammatory response and often multi-organ failure. Mortality varies from 20 to 50%.

73. Etiology of Acute PANCREATITIS Gallstones (50-70%) Alcoholism (20-25%) Post ERCP Abdominal trauma Following biliary, upper gastrointestinal or cardiothoracic surgery Ampullary tumour Drugs (corticosteroids, azathioprine, asparaginase, valproic acid, thiazides, oestrogens )

74. Etiology of Acute PANCREATITIS Hyperparathyroidism Hypercalcaemia Pancreas divisum Autoimmune pancreatitis Hereditary pancreatitis Viral infections (mumps, coxsackie B) Malnutrition Scorpion bite Idiopathic

75. GALL STONE PANCREATITIS: COMMON CHANNEL THEORY Stone lodged at ampulla of vater results in bile reflux into pancreatic duct. After passage of gall stone through sphincter of oddi , it becomes incompetent and results in reflux of duodenal fluid and bile into pancreatic duct.

76. GALL STONE PANCREATITIS: Gall stone blocking pancreatic duct ductal hypertension Increase Back pressure in pancreatic duct leads to minor ductal disruption Extravasation of pancreatic secretions into parenchyma Premature enzyme activation

77. ALCOHOL PANCREATITIS: Excessive alcohol consumption 100-150 gm/day; Ethanol content in alcohol is toxic to acinar cells causing increased secretion followed by inhibition. Ethanol causes spasm of sphincter of oddi .

78. ALCOHOL PANCREATITIS: Ethanol induced increased duct permeability allows premature activation of enzymes causing damage to pancreatic parenchyma. Ethanol increases protein content of the pancreatic juice and protein plug formation in the pancreatic duct causing obstruction.

79. PATHOPHYSIOLOGY Once cellular injury has been initiated the inflammatory process can lead to- Pancreatic edema Pancreatic haemorrhage Pancreatic necrosis

80. PATHOPHYSIOLOGY As inflammatory mediators are released into circulation, systemic complications can occur Hemodynamic instability Bacteremia ARDS Pleural effusion Gastrointestinal hemorrhage Renal failure DIC

81. PATHOPHYSIOLOGY

82. Acinar cell events Normally pro-enzymes which are inactive in pancreas turns into active form in the duodenum. Trypsinogen converted to trypsin in the duodenum. Trypsin converts other pro-enzymes into active form.

83. SIRS Pancreatitis

84. Acinar cell events INSULT Sustained Rise in Ca2+ ZYMOGEN GRANULES Trypsinogen LYSOSYMES cathepsin B Colocalization Cathepsin B ↓ Trypsinogen → TRYPSIN Colocalization Cathepsin B ↓ Trypsinogen → TRYPSIN Acinar cell death

85. Acinar cell events Sustained Rise in Ca2+ Lysosomal (L) and zymogen (Z) contents colocalize trypsinogen is activated to trypsin by cathepsin B trypsin ↑ permeability cathepsin B released in to cytosol cytochrome c released from the mitochondria apoptosis

86. Acinar cell events INSULT ↑ Ca2+ NF–KB activation PKC activation Release of Cytokines and Chemokines SYSTEMIC INFLAMMATION SIRS → MODS → DEATH

87. Acinar cell events protein kinase c enzyme nuclear factor kappa and beta( nfkb ) release of cytokines and chemokines systemic inflammatory response (sirs) Mods death

88. CLINICAL MANIFESTATIONS SYMPTOMS: Epigastric pain, Sudden onset, radiating to the back (50%) with nausea and vomiting. Pain is frequently severe, constant and refractory to the usual doses of analgesics. Discomfort may be relieved by sitting or bending forward and aggravated by lying down.

89. CLINICAL MANIFESTATIONS SIGNS: Abdominal tenderness. Abdominal Distension (d/t Ileus) Guarding In Upper abdomen Severe pancreatitis may lead to retroperitoneal hemorrhage which leads to : 1 . Hypovolemia 2. Hypotension 3. Tachycardia

90. CLINICAL MANIFESTATIONS SIRS is defined by the presence of two or more of the following criteria: heart rate >90/min, core temperature <36 o C or >38 o C, respirations >20/min or pCO2 <32 mmHg, and white blood cell count <4000 or >12 000/mm3.

91. Cullen’s sign (periumbilical ecchymosis) Grey Turner’s sign (flank ecchymosis) CLINICAL MANIFESTATIONS

92. Differential diagnosis Acute cholecystitis Perforated duodenal ulcer Acute myocardial infarction pneumonia or pleuritic pain.

93. ASSESMENT OF SEVERITY It is done by various scoring systems: BISAP Scoring System ( B edside I ndex of S everity in A cute P ancreatitis) RANSONS Scoring System Glasgow Scoring System APACHE I , APACHE II, APACHE III ( A cute P hysiologic A ssesment and C hronic Health E valuation) CT Severity Index (CTSI) Balthazar Grading System (CT)

94. ASSESMENT OF SEVERITY

95. ASSESMENT OF SEVERITY Atlanta classification of acute pancreatitis be stratified into 3 groups: Mild acute pancreatitis : no organ failure; no local or systemic complications. Moderately severe acute pancreatitis: organ failure that resolves within 48 hours (transient organ failure);/ local or systemic complications without persistent organ failure. Severe acute pancreatitis: persistent organ failure (>48 hours); single organ failure; multiple organ failure.

96. DIAGNOSIS ROUTINE INVESTIGATIONS- CBC. Hematocrit, RFT, LFT, LDH, Se Electrolytes and calcium, ABG , CXR, ECG SPEIFIC INVESTIGATIONS: Serum amylase – Increased in 95% of cases; 5% false negative, Not indicator of severity. Level over 1,000 Somogyi-Nelson units Urine Amylase- Elevated Serum Lipase – Elevated 99% Cases

97. DIAGNOSIS URINARY TRIPSINOGEN 2

98. DIAGNOSIS URINARY TRIPSINOGEN-2 Amylase Lipase Positive 35 30 34 Negative 3 1 2 False Positive 1 5 2 False Negative 3 1

99. RADIOLOGICAL INVESTIGATIONS X-ray Abdomen- Colon Cut Off Sign Ultrasound – Swelling of the pancreas and loss of tissue planes. CT scan – Obliteration of fat strands, edema, necrotic areas.

100. Abrupt cut off of colonic gas column at splenic flexure- colon cutoff sign Colon beyond this point is decompressed by normal peristalsis

101. CT SCAN INDICATIONS If there is diagnostic uncertainity . In severe acute pancreatitis. Patient with organ failure, signs of sepsis or progressive clinical deterioration. When localized complication is suspected such as fluid collection, pseudocyst or pseudo aneurysm.

102. CT SCAN INDICATIONS

103. BALTHAZAR CT SCAN SCORING SYSTEM OF ACUTE PANCREATITIS CT GRADE PATHOLOGY POINTS A NORMAL B OEDEMATOUS 1 C MILD EXTRAHEPATIC COLLECTION 2 D SEVERE EXTRAHEPATIC COLLECTION 3 E EXTENSIVE/MULTIPLE EXTRAHEPATIC COLLECTION 4

104. Management of pancreatitis is PANCREAS

105. MANAGEMENT –MILD ATTACK P - PAINKILLERS A - ANTIBIOTICS N - NASOGASTRIC-ASPIRATION C - CALCIUM-GLUCONATE R - REPLACEMENT-FLUIDS E - ENZYME - REPLACEMENT A - ANTI-CHOLINERGICS S - STOMATOSTATIN ANALOGUES

106. MANAGEMENT –SEVERE ATTACK Admission to HDU/ICU Analgesia Aggressive fluid rehydration Oxygenation 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)

107. MANAGEMENT –SEVERE ATTACK Nasogastric drainage Antibiotic prophylaxis can be considered ( imipenem , cefuroxime ) 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.) Nutritional Support

108. KEY POINTS TO REMEMBER IT IS ESSENTIAL TO ESTABLISH THE ETIOLOGY . INVESTIGATE THOROUGHLY BEFORE LABELLING IT AS IDIOPATHIC. IF THE ETIOLOGY IS GALL STONES,CHOLECYSTECTOMY IS DESIRABLE DURING THE SAME ADMISSION. SURGICAL INTERVENTIONS IN ACUTE PANCREATITIS IS RESERVERD FOR COMPLICATIONS.

109. COMPLICATIONS OF PANCREATITIS DEVELOP AFTER THE FIRST WEEK COMMON WITHIN THE FIRST WEEK

110. COMPLICATIONS SYSTEMIC ( More common in the first week ) Cardiovascular -Shock -Arrhythmias Pulmonary -ARDS Renal failure Haematological -DIC Metabolic - Hypocalcaemia,hyperglycemia,hyperlipidemia .

111. SYSTEMIC COMPLICATIONS Gastrointestinal -Ileus Neurological -Visual disturbances -Confusion, irritability -Encephalopathy Miscellaneous -Subcutaneous fat necrosis -Arthralgia

112. SYSTEMIC COMPLICATIONS Pancreatitis may involve all organ systems should be managed by a multidisciplinary team inotropic support for haemodynamic instability, haemofiltration in the event of renal failure, ventilatory support for respiratory failure correction of coagulopathies (including DIC) There is no role for surgery during the initial period of resuscitation and stabilisation

113. LOCAL COMPLICATIONS (usually develop after 1 st week): Acute fluid collection Sterile pancreatic necrosis Infected pancreatic necrosis Pancreatic abscess Pseudocyst Pancreatic ascites Pleural effusion Portal/splenic vein thrombosis Pseudoaneurysm

114. ACUTE PERIPANCREATIC FLUID COLLECTION (APFC) occurs early in the course of mild pancreatitis without necrosis located adjacent to the pancreas No encapsulating wall and is confined within normal fascial planes The fluid is sterile No intervention is necessary large collection causes symptoms or pressure effects Percutaneously aspirated under ultrasound or CT guidance. Transgastric drainage under EUS guidance

115. PANCREATIC NECROSIS ‘pancreatic necrosis’ refers to a diffuse or focal area of non-viable parenchyma CECT – absence of parenchymal enhancement Pancreatic necrosis lysis of peripancreatic fat acute necrotic collection (ANC) well-defined inflammatory capsule walled-off necrosis (WON) 4 weeks

116. PANCREATIC NECROSIS necrotising pancreatitis are sterile due to translocation of gut bacteria become subsequently infected necrosis mortality rate – 50% Sterile necrotic material should not be drained

117. PANCREATIC NECROSIS

118. PANCREATIC NECROSIS Infected pancreatic necrosis be drained Either CT or USG Guided If the sepsis worsens → pancreatic necrosectomy debridement of the dead tissue around the pancreas high morbidity and mortality Either Open or Laparoscopic

119. PANCREATIC NECROSIS After necrosectomy further necrotic tissue may form. There are several possible ways of dealing with this Closed continuous lavage Closed drainage Open packing Closure and relaparotomy

120. Closed continuous lavage Tube drains are left in and the raw area flushed ( Beger ) Continuous postoperative closed lavage of the lesser sac as advised by Beger . Lavage is carried out through several double-lumen and single-lumen catheters. Each time, 1 litre of saline is infused through and then drained over a period of hours, and the process is repeated.

121. PANCREATIC NECROSIS Closed drainage The incision is closed, but the 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.

122. PANCREATIC NECROSIS Open packing The incision is left open Cavity is packed with the intention of returning to the operating room at regular intervals repacking until there is a clean granulating cavity.

123. PANCREATIC NECROSIS Closure and relaparotomy The incision is closed with drains with the intention of performing a series of planned relaparotomies every 48–72 hours until the raw area granulates (Bradley).

124. PANCREATIC ASCITES IT’S THE COLLECTION OF ENZYME RICH FLUID IN PERITONEAL CAVITY DUE TO PANCREATIC DUCT DISRUPTION. PARACENTESIS REVEAL HIGH AMYLASE LEVEL. OCTREOTIDE IS USED TO SUPPRESS THE PANCREATIC SECRETION. ERCP DONE TO FIND OUT ANY PANCREATIC DUCT DISRUPTION AND PLACEMENT OF STENT.

125. HAEMORRHAGE OCCURS FOLLOWING AN ATTACK OF PANCREATITIS DUE TO BLEEDING FROM PSEUDANEURYSM OR PSEUDOCYST. HAEMORRHAGE OCCURS INTO GIT. WHEN BLEEDING OCCURS INTO PANCREATIC DUCT IT IS CALLED HAEMOSUCCUS PANCREATICUS .

126. THIS CONDITION OCCURS DUE TO ENZYMATIC DIGESTION OF BLOOD VESSELS IN VICINITY OF PANCREAS. USUALLY SPLENIC OR GASTRODUODENAL ARTERY INVOLVED. IT HAS HIGH MORTALITY TREATMENT: CT ANGIOGRAPHY FOLLOWED BY EMBOLIZATION. IF NOT POSSIBLE OPEN LAPAROTOMY AND LIGATION OF PSEUDOANEURYSM OR BLEEDING VESSELS IN THE CAVITY.

127. PSEUDOCYST COLLECTION OF AMYLASE RICH FLUID IN LESSER SAC DUE TO PANCREATIC PATHOLOGY. IT IS CALLED PSEUDOCYST BECAUSE IT HAS NO EPITHELIAL LINING. IF FLUID COLLECTION OCCURS WITHIN 4 WEEKS OF AP ITS CALLED ACUTE FLUID COLLECTION. AFTER 4 WEEKS OF AP, FLUID COLLECTION IS CALLED PSEUDOCYST.

128. CAUSES ACUTE PANCREATITIS PANCREATIC INJURY CHRONIC PANCREATITIS

129. LOCATION BETWEEN STOMACH AND TRANSVERSE COLON BETWEEN STOMACH AND LIVER BEHIND OR BELOW THE TRANSVERSE COLON.

130. D’EGIDIO CLASSIFICATION OF PSEUDOCYST TYPE 1-OCCURS AFTER ACUTE PANCREATITIS WITH NORMAL PANCRETIC DUCT ANATOMY. HERE PSEUDOCYST WILL NOT HAVE COMMUNICATION WITH PD. TYPE 2-OCCURS AFTER ACUTE PANCREATITIS WITH DISEASED PD. HERE CYST COMMUNICATES WITH PD. TYPE 3-OCCURS IN CHRONIC PANCREATITIS. HERE STRICTURE PD AND CYST COMMUNICATES WITH THE PD.

131. CLINICAL FEATURES TENSE CYSTIC MASS IN THE EPIGASTRIC, UMBLICAL REGION EXTENDING INTO LEFT HYPOCHONDRIUM. MASS DOES NOT MOVE WITH RESPIRATION, IT DOES NOT FALL FORWARD. TRANSMITTED PULSATION FROM AORTA CAN BE FELT. BAID SIGN: IF RYLES TUBE IS PASSED IT CAN BE FELT OVER THE SWELLING.

132. INVESTIGATIONS ULTRASOUND CT ENDOSCOPIC USG (DIAGNOSTIC & THERAPEUTIC) ERCP, MRCP –to know whether cyst is communicating with PD

133. DIFFERNTIAL DIAGNOSIS PSEUDOCYST SHUD BE DIFFERENTIATED FROM CYSTIC NEOPLASM OF PANCREAS. ASPIRATE THE FLUID AND SEND FOR ANALYSIS OF CEA,AMYLASE ESTIMATION AND CYTOLOGY.

134. COMPLICATIONS PSEUDOCYST RESOLVES SPONTANEOUSLY IN MAJORITY OF CASES. PSEUDOCYST WITH THICK WALL > 6 cms ,IF CYST PRESENT FOR > 12 weeks AND IF IT IS DUE TO CHRONIC PANCRETITIS THEY ARE LESS LIKELY TO RESOLVE.

135. Possible complications of a pancreatic pseudocyst PROCESS OUTCOMES INFECTION ABSCESS SYSTEMIC SEPSIS RUPTURE -INTO THE GUT -INTO THE PERITONEUM GASTROINTESTINAL BLEEDING INTERNAL FISTULA PERITONITIS ENLARGEMENT -PRESSURE EFFECTS -PAIN OBSTRUCTIVE JAUNDICE FROM BILIARY COMPRESSION BOWEL OBSTRUCTION EROSION INTO A VESSEL HAEMORRHAGE INTO THE CYST HAEMOPERITONEUM

136. TREATMENT DRAINAGE OF PSEUDOCYST OF PANCREAS: PERCUTANEOUS DRAINAGE ENDOSCOPIC DRAINAGE SURGICAL

137. PERCUTANEOUS DRAINAGE PERCUTANEOUS TRANS GASTRIC CYSTOGASTROSTOMY IS DONE UNDER IMAGING GUIDANCE. HERE DOUBLE PIGTAIL DRAIN,ONE END IN CYST CAVITY AND OTHER END IN GASTRIC LUMEN.

138. ENDOSCOPIC DRAINAGE USUALLY INVOLVES PUNCTURE OF CYST THROUGH STOMACH OR DUODENAL WALL. UNDER EUS GUIDANCE AND PLACEMENT OF TUBE DRAIN-ONE IN THE CAVITY AND OTHER IN THE LUMEN.

139. SURGICAL INTERNAL DRAINAGE OF PSEUDOCYST, CYSTO-GASTROSTOMY CYSTO-JEJUNOSTOMY

140. CYSTO-GASTROSTOMY

141. CYSTO-JEJUNOSTOMY

142. Chronic pancreatitis progressive inflammatory disease with irreversible destruction of pancreatic tissue. clinical course severe pain later stages, exocrine and endocrine pancreatic insufficiency southern India, the prevalence is much higher (100–200 per 100 000). male: female ratio of 4:1 mean age of onset is about 40 years

143. Chronic pancreatitis Pancreas becomes small, indurated and nodular and edges become rounded. Alternating areas of strictures and dilatations in the duct with calcifications. More of a clinical diagnosis than pathological diagnosis

144. Chronic pancreatitis ETIOLOGY Genetic mutations, Alcohol exposure, Duct obstruction due to trauma, gallstones, and tumors , Metabolic diseases such as hyperlipidemia and hyperparathyroidism, Auto-immune disease. Tropical pancreatitis

145. Chronic pancreatitis

146. TIGAR-O Classification System for Chronic Pancreatitis Toxic-Metabolic Idiopathic Genetic Autoimmune Recurrent and Severe Acute Obstructive Alcoholic Tobacco smoking Hypercalcemia Hyperlipidemia Chronic renal failure Medications Toxins Early onset Late onset Tropical (tropical calcific and fibrocalculous pancreatic diabetes) Other Autosomal dominant: cationic trypsinogen gene –(PRSS1 gene) Autosomal recessive: CFTR mutations, SPINK1 mutations, cationic trypsinogen α1- antitrypsin deficiency Isolated autoimmune chronic pancreatitis Syndromic autoimmune chronic pancreatitis Eg:Sjogren syndrome– associated Vascular disease/ ischemic Radiation injury Postnecrotic (severe acute pancreatitis) Pancreas divisum Duct obstruction (e.g., tumor) Posttraumatic pancreatic duct scars

147. Chronic pancreatitis Alcohol (drunkard’s pancreas) 60–70% of cases highest in heavy (>150 g/d) drinkers Pathology is unclear Repeated inflammation genetic and metabolic factors may play a role

148. Tropical pancreatitis form of idiopathic pancreatitis begins at a young age high incidence of diabetes mellitus and stone formation High incidence in Kerala. mechanisms for tropical pancreatitis Malnutrition, ingestion of cyanogenic glycosides in cassava Root , exposure to hydrocarbons released by kerosene or paraffin lamps

149. Tapioca / Cassava/ Sweet potato

150. GENETIC FACTORS IN DEVOLOPMENT OF CHRONIC PANCREATITIS PRSS-1 [Protease serine -1] Chromosome 7 mutation of cationic trypsinogen gene leads to loss of autoregulation of trypsin Mutant trypsin activate other proenzyme and produce clinical & subclinical episodes of AP and ultimately leads to chronic pancreatitis.

151. SPINK-1[serine protease inhibitor kazal type-1] gene mutation leads to non inhibition of trypsin -- producing clinical or sub clinical episode of acute pancreatitis >> chronic pancreatitis. CFTR gene – Cystic Fibrosis Trasmembrane conductance Regulator gene All the above genetic factors lead to development of Hereditary (AD) and Idiopathic pancreatitis

152. AUTOIMMUNE PANCREATITIS Autoimmune pancreatitis may occur in association with other autoimmune diseases as Multiple system disorder or may affect the pancreas alone eg : Sjogrens syndrome, Primary biliary cirrhosis, primary sclerosing cholangitis. Autoantibodies may be present and level of the immunoglobulin sub type IgG4 are elevated.

153. Pathology Chronic pancreatitis

154. In chronic pancreatitis repeated episodes of acinar cell injury lead to pro fibrogenic cytokines Transforming growth factor –beta[TGF-B] Platelet-derived growth factor[PDGF] Both TGF-B and PDGF induce activation and proliferation of pancreatic stellate cells resulting in the deposition of collagen and fibrosis

155. Pathology Chronic pancreatitis “ Multiple hit” theory of the etiology of chronic pancreatitis. Multiple episodes of acute pancreatitis cause progressively more organized inflammatory changes that ultimately result in chronic inflammation and scarring.

156. Chronic Calcific Pancreatitis Chronic Obstructive Pancreatitis Chronic Inflammatory Pancreatitis Chronic Autoimmune Pancreatitis Asymptomatic Pancreatic Fibrosis Alcohol Hereditary Tropical Hyperlipidemia Hypercalcemia Drug-induced Idiopathic Pancreatic tumors Ductal stricture Gallstone- or trauma induced pancreas divisum Unknown Associated with autoimmune disorders (e.g., primary sclerosing cholangitis) Sjögren's syndrome Primary biliary cirrhosis Chronic alcoholic Endemic in asymptomatic residents in tropical climates

157. CLINICAL MANIFESTATIONS History of alcoholism and recurrent attacks of pancreatitis Pain-radiating to back Diabetes steatorrhea. Frequent associated with pseudocyst. Anorexia and weight loss

158. Pain location in chronic pancreatitis

159. PATIENT LEANS FORWARD WITH PAIN

160. STEATORRHEA It is the presence of excess fat in feaces . Stools are bulky and difficult to flush. Steatorrhea does not occur until pancreatic lipase secretion is reduced to less than 10% of maximum out put It is a feature of far advanced pancreatitis

161. INVESTIGATIONS Pancreatic Function Tests- Decreased function and Pancreatic Insufficiency Xray Abdomen- Pancreatic Calcifications USG Abdomen- Pancreatic Calcifications, Pseudocysts and decreased gland size

162. INVESTIGATIONS CT Abdomen- The main area of damage and the possibilities for surgical correction MRCP - Will identify the presence of biliary obstruction and the state of the pancreatic duct . ERCP- Most accurate way of elucidating the anatomy of the duct and, in conjunction with the whole organ morphology, can help to determine the type of operation required.

163. MRCP (Magnetic Resonance Cholangio Pancreaticography ) Non invasive Asses pancreatic parenchyma and ducts at the same time It can detct pancreatic ductal dilatation, filling defects and narrowing

164. DILATED PANCREATIC DUCT WITH CALCIFICATIONS

165. ERCP (Endoscopic Retrograde Cholangio Pancreaticography) Provides most accurate visualization of the pancreatic ductal system Gold standard for the diagnosis of chronic pancreatitis Findings include Chain of lakes - Beading of the main pancreatic duct Intra ductal filling defects

166. ERCP in a patient with chronic pancreatitis shows calcifications in the region of the pancreatic head and concomitant distal common bile duct stenosis.

167. Pancreatogram shows a dilated and tortuous pancreatic duct with multiple side branches.

168. Endoscopic ultrasonography (EUS) visualizes both the pancreatic ducts and the parenchyma EUS has the ability to detect CP in patients with early stage EUS features of CP include ductal and parenchymal changes

169. The presence of four or more of these features is highly suggestive of chronic pancreatitis Parenchymal abnormality hyperechoic foci hyperechoic strands Lobularity of contour Cysts Ductal Abnormilities Main duct dilatation Main duct irregularity Hyperechoic ductal wall Visible side duct calcification

170. Calcifications of Chronic Pancreatitis

171. Calcifications of Chronic Pancreatitis

172. MEDICAL MANAGEMENT -Treat the Alcohol addiction -Alleviate abdominal pain Eliminate obstructive factors (duodenum, bile duct, pancreatic duct) Escalate analgesia in a stepwise fashion For intractable pain, consider CT/EUS-guided coeliac axis block

173. MEDICAL MANAGEMENT Nutritional and digestive measures Diet: low in fat and high in protein and carbohydrates Pancreatic enzyme supplementation with meals Correct malabsorption of the fat-soluble vitamins (A, D, E,K) and vitamin B12 Medium-chain triglycerides in patients with severe fat malabsorption (they are directly absorbed by the small intestine without the need for digestion) Reducing gastric secretions Treat diabetes mellitus

174. Endoscopic management Papillary stenosis: Pancreatic duct sphincterotomy will facilitate drainage Pancreatic duct stricture: Sphincterotomy , dilatation and stent placement Pancreatic duct calculi: Sphincterotomy , dilatation and stone extraction with stenting.

175. SURGICAL MANAGEMENT Drainage procedure Lateral Pancreaticojejunostomy ( puestow’s procedure) Lateral Pancreaticojejunostomy ( Partington – Rochelle operation– Spleen is preserved) Resective procedure Whipple’s procedure Distal pancreatectomy Total pancreatectomy Pancreatoduodenectomy or a Beger procedure (duodenum-preserving resection of the pancreatic head) – If mass is there at the head of pancreas Decoring of head of pancreas with pancreatojejunostomy or Frey procedure- if duct is dilated or multiple calculi are present

176. Puestow’s procedure Lateral Pancreaticojejunostomy Tail of the pancreas is removed along with Spleen

177. Partington – Rochelle operation Lateral Pancreatico jejunostomy (Spleen is preserved)

178. Frey procedure Decoring of head of pancreas with pancreatojejunostomy

179. Beger procedure ( Duodenum-preserving pancreatic head resection (DPPHR) )

180. Prognosis The overall survival rate is 70% at 10 years and 45% at 20 years The risk of developing pancreatic cancer is approximately 4% at 20years

181. CARCINOMA PANCREAS Exocrine tumors Pancreatic Ductal Adenocarcinoma Pancreatoblastoma Acinar Cell Carcinoma Intraductal Papillary Mucinous Neoplasms Mucinous Cystic Neoplasms Solid-Pseudopapillary Neoplasms Endocrine tumors Insulinoma (β cells) Whipple’s triad Gastrinoma (G cells) Peptic ulcer. Glucagonoma ( α cells) Diabetes, necrolytic migratory erythema. Vipoma —Pancreatic Watery diarrhoea , cholera (Verner- hypokalaemia Morrison syndrome) achlorhydria. (WDHA syndrome) Somatostatinoma . Diabetes, (S cells) δ cells steatorrhoea , gallstones.

182. 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

183. PATHOLOGY Cystadenoma / Cystadenocarcinoma : SEROUS TYPE ( Benign) a. Rare; predilection for females b. Cystic spaces divided by fibrous septa; vascular c. Better prognosis than adenocarcinoma d. Tx . - Resection

184. MUCINOUS TYPE: They include : Mucinous cystic neoplasms (MCNs) Intraductal papillary mucinous neoplasms(IPMNs). MCN s are Seen in perimenopausal women, Consists of multilocular thick-walled cysts in the pancreatic body or tail Histologically, contain an ovarian type stroma .

185. INTRADUCTAL PAPILLARY MUCINOUS NEOPLASMS (IPMNS) IPMNs are 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 tendencyto prove malignant

186. 2 . ADENOCARCINOMA (DUCTAL) a. 90% of cases; usually at the head. b. Periampullary malignancy i . Head of the pancreas – 83% ii. Ampulla of Vater – 10% iii. Duodenum – 4% iv. Common bile duct – 3% c. Solid, scirrhous tumours, characterised by neoplastic tubular glands within a markedly desmoplastic fibrous stroma .

187. CLINICAL MANIFESTATIONS Weight loss – most common Pain – dull epigastric pain that radiates to the back; aggravated by eating and upper abdominal discomfort Progressive jaundice – 75% secondary to obstruction of the distal bile duct is the most common symptom

188. Anorexia and weakness, new onset diabetes Pruritus, dark urine and pale stools with steatorrhoea Obstructive jaundice. Enlarged palpable gallbladder – Courvesiure’s Law IN A JAUNDICED PATIENT- PALPABLE GALL-BLADDER IS SELDOM DUE TO STONES

189. INVESTIGATIONS Alkaline PO4 GGT SGOT SGPT Direct Bilirubin Total Bilirubin Urobilinogen The tumour marker CA19-9 is not highly specific or sensitive

190. INVESTIGATIONS USG : Increased Size of Pancreas and Dilated ducts with occasional findings of well defined mass/ Cystic mass ENDOSCOPY : Can visualize growth at the periampullary region in second part of duodenum and biopsy can also be taken . ENDOSCOPIC ULTRASOUND : Can demonsrate vascular invasion and can seperate cystic tumours from pseudocysts Transduodenal or transgastric FNA or Trucut biopsy can performed under EUS guidance

191. PERIAMPULLARY GROWTH ON ENDOSCOPY

192. CARCINOMA PANCREAS ON EUS

193. INVESTIGATIONS CECT ABDOMEN : Can establish if there is a tumour in the pancreas and if it is resectable or not. Presence of hepatic or peritoneal metastases or lymph node metastases distant from the pancreatic head Encasement of the superior mesenteric, hepatic or coeliac vessels MRI AND MR VENOGRAPHY : Similar information as CT

194. CT- DEMONSTRATING RESECTABLE PANCREATIC CANCER

195. ERCP: It is indicated(along with Biliary stenting) when Suspicion of Cholangitis Diagnostic Confirmation Relieve Jaundice if Surgery is delayed Palliative stenting in inoperable cases

196. American Joint Committee on Cancer Staging for Pancreatic Cancer (Eighth Edition)

197. American Joint Committee on Cancer Staging for Pancreatic Cancer (Eighth Edition)

198. MANAGEMENT On presentation >85% tumors are not resectable . Resectbility is assesed by: Hepatic or peritoneal metastases, Lymph node metastases distant from the pancreas Encasement of the Major Vessels Tumour size, Continuous invasion of the duodenum, stomach or colon, Lymph node metastases within the operative field NO RESECTION NO CONTRA- INDICATION

199. SURGICAL TREATMENT WHIPPLES PROCEDURE : It involves removal of tumor with head and neck of pancreas, C loop of duodenum, distal stomach, proximal jejunum, lower end of the common bile duct, gallbladder and involved lymph nodes It consists of 3 main steps: Choledochojejunostomy Pancreaticojejunostomy Gastrojejunostomy

200. pancreaticoduodenectomy (Whipple procedure) VS pylorus-preserving pancreatoduodenectomy (PPPD)

201. Adequate nutritional preparation of the patient preoperatively Close post operative monitoring Parenteral nutrition post operatively Watch for complications like pancreatic fistula, leak of the anastomotic site etc… Prevent post op complications like DVT , Atelectasis Follow up with Chemotherapy after surgery

202. PALLIATIVE THERAPY Relieve jaundice and treat biliary sepsis Surgical biliary bypass Stent placed at ERCP or PTBD Improve gastric emptying Surgical gastroenterostomy Duodenal stent Pain relief Stepwise escalation of analgesia Coeliac plexus block

203. PERCUTANEOUS TRANS HEPATIC BILIARY DRAINAGE

204. Symptom relief and quality of life Encourage normal activities Enzyme replacement for steatorrhoea Treat diabetes 5-FU/gemcitabine based chemotheraphy . External beam radiation- rarely used due toxicity of vital organs around the pancreas.

205. THANK YOU