Chronic pancreatitis

etiology,clinical features of chr.pancreatitis,medical management,reason for pain,indications of LPJ

1. Chronic pancreatitis & Indications for LPJ Discussion - G.P.Chakravarthy ( Gen.Surgery PG) Moderators - Dr.A.Satish Babu sir (Prof. in Gen.Surgery ) Dr.Viswanath sir ( Asst.Prof in GenSurgery )

2. Anatomy Weight : 75 - 125 g Size : 10 to 20 cm It lies in the retro peritoneum just anterior to the first lumbar vertebrae Anatomically divided into four portions, the head, neck, body and tail.

3. Pancreatic ducts Main duct of pancreas ( Duct of Wirsung ): It begins in the tail of pancreas and runs along its posterior surface , receives numerous tributaries at right angle along its length (‘ Herring bone pattern’). It joins the bile duct to form hepatopancreatic ampulla (of Vater ) Accessory pancreatic duct (Duct of Santorini ): It begins in the lower part of the head opens into the duodenum at minor duodenal papilla (6-8 cm from the pylorus).

4. Arterial supply

5. Nerve supply

6. Chronic Pancreatitis Definition : it is a benign inflammatory process and fibrosing disorder characterized by irreversible morphologic changes, Progressive and permanent loss of exocrine and endocrine function

7. Chronic Pancreatitis Clinically, the disease is characterized by recurrent episodes of severe and uncontrollable upper abdominal pain and by a loss of exocrine function (diarrhea, steatorrhea ) and endocrine function (diabetes mellitus)

8. Chronic Pancreatitis Incidence – 3-10 / 1lakh population More common in men Middle aged > 40 yrs 2/3 rds are alcoholics

9. Etiology – (TIGAR –O classification) Toxic – Metabolic Idiopathic Genetic / hereditary Autoimmune / immunologic Recurrent acute pancreatitis Obstructive / mechanical

10. Toxic / metabolic alcohol consumption 60 – 90 % Tobacco (changes in composition , oxidative stress) Hypercalcemia ( trypsinogen & trypsin stabilisation , calculi formation , direct acinar cell injury) CRF – uremia

11. Idiopathic Up to 20 % of patients with CP have no known risk factors Based on the bimodal age of onset of the clinical symptoms – 2 distinct entities Early onset idiopathic CP - first 2 decades of life, abdominal pain - predominant clinical feature, pancreatic calcifications and exocrine and endocrine pancreatic insufficiency are very rare at the time of diagnosis

12. Idiopathic Late onset idiopathic CP : Fifth decade of life, Usually painless course associated with significant exocrine and endocrine pancreatic insufficiency and Pancreatic calcifications

13. Tropical pancreatitis Tropical pancreatitis is one of the most common forms of chronic pancreatitis in certain areas of southwest India. Tropical pancreatitis is generally a disease of youth and early adulthood, with a mean age at onset of 24 years . The disease classically manifests as abdominal pain, severe malnutrition, and exocrine or endocrine insufficiency.

14. Genetic factors / hereditary : CFTR : Cystic fibrosis is assosiated with ductal dilatation, precipitate formation, pancreatic atrophy PRSS1 : chromosome 7 and regulates trypsinogen production; mutations - intra- acinar trypsinogen activation - resistant to inactivation - activate other proenzymes - episodes of acute pancreatitis – chronic pancreatitis

15. Genetic factors / hereditary : 3 . SPINK 1 - serine protease inhibitor Kazal type 1 regulates the premature activation of trypsinogen SPINK1 mutations are not enough to trigger pancreatic inflammation. they lower the threshold for its development and influence the severity of the disease.

16. Auto immune / immunological rare but distinct form of CP characterized by specific histopathologic and immunologic features Autoimmune diseases , viral infections ( coxsackie ) hallmarks are periductal infiltration by lymphocytes and plasma cells granulocytic epithelial lesions & destruction of the duct epithelium venulitis

17. Auto immune / immunological minimal abdominal pain diffuse enlargement of the pancreas without calcifications or pseudocysts most commonly involves the head of the pancreas and the distal bile duct.

18. Obstructive scars of the pancreatic duct, tumors of the ampulla of Vater & head of the pancreas, Trauma Main pancreatic duct obstruction may lead to stagnation and stone formation by pancreatic juice Leads to recurrent pancreatitis – periductal fibrosis - chronic pancreatitis

19. Pathogenesis Protein Plug hypothesis : Alcohol Protein conc in pancreatic secretion & Glycoprotein2 secretions in acinar cells formation of protein precipitates & protein plug calcification of ppt. ductal stone formation duct obstruction Ulceration of epithelium , fibrosis

20. Pathogenesis Toxic metabolite hypothesis : fatty acid ethyl esters and reactive O2 species Increase fragility in intraacinar oraganelles such as zymogen granules and lysosomes , Damage acinar cells scarring of the pancreatic parenchyma Impair microcirculation Acetaldehyde causes direct acinar injury.

21. Pathogenesis Pancreatic stellate cells (PSCs) : PSCs – quiescent fibroblasts (base of acinar cells.) PDGF, TNF, IL-1, IL-6 Alcohol & its metabolites activated myofibroblasts Synthesize proteins (collagen I and III, fibronectin , laminin,MMP ) FIBROSIS

22. pathogenesis Primary duct hypothesis : immune reactions cause – periductal inflammation – scarring of the ducts – outflow obstruction - destruction and fibrosis

23. Clinical features Abdominal Pain Exocrine insufficiency occurs in 80% to 90 % steatorrhea , diarrhea, fat-soluble vitamin deficiency, such as bleeding, osteopenia , and osteoporosis, Endocrine insufficiency - diabetes mellitus Jaundice or cholangitis Rarely upper GI bleed

24. Abdominal Pain most common and most debiliating Initially pain manifests after consumption of food , later on it becomes continuous and affects quality of life Loses apetite , wt loss , addiction to narcotic analgesics

25. Abdominal Pain epigastrium , often with radiation to the back . boring, deep, and Penetrating relieved by leaning forward, by assuming the knee-chest position on 1 side Loses apetite , wt loss , addiction to narcotic analgesics ,

26. Abdominal Pain Proposed 2 mechanisms for pain increased pressure and ischemia injury and alterations in peripheral and central nociceptive nerves

27. Pain increased pressure and ischemia : Obstruction in ducts leads to Increased pressure Similar to compartment syndrome where increased pressure leads to ischemia which causes pain Proven in animal studies and decreased Pancreatic blood flow, measured at ERCP and basis for surgical intervention

28. Pain Alterations in Peripheral and Central Nociceptive Nerves : Demonstrated increase in the diameter and number of intrapancreatic nerves, foci of inflammatory cells associated with nerves and ganglia, and damage to the perineural sheath The disruption of the perineural sheath may allow inflammatory mediators to gain access to the neural elements.

29. Pain The accumulation of inflammatory mediators and nerve injury can sensitize the nerve, making it hyper-responsive Chronic pain due to chronic peripheral nerve injury or inflammation leads to changes in nociceptive processing that involve both the spinal cord and CNS . Chronic pain can produce a centrally sensitized pain state in which elimination of the original source of pain does not relieve pain

30. Exocrine insufficiency : Steatorrhea and azotorrhea (protein maldigestion ) do not usually occur until pancreatic enzyme secretion is reduced to less than 10% of the maximum output Advanced chronic pancreatitis, maldigestion of fat, protein, and carbohydrates occur - present with diarrhea and weight loss median time to development of exocrine insufficiency was 13.1 years in patients with alcoholic chronic pancreatitis

31. Exocrine insufficiency : Deficiencies of fat-soluble vitamins Significant vitamin D deficiency and osteopenia or even osteoporosis occur Bleeding manifestations

32. Endocrine insufficiency : Chronic pancreatitis also affects islet cell populations - 40% to 80% of patients will have clinical manifestations of diabetes mellitus Islet cells appear to be relatively resistant to destruction in chronic pancreatitis - Diabetes mellitus typically manifests late

33. Extrapancreatic complications Jaundice may be seen in the presence of coexistent alcoholic liver disease or bile duct compression within the head of the pancreas. & duodenal obstruction A palpable spleen may also rarely be found in patients with thrombosis of the splenic vein as a consequence of chronic pancreatitis or in patients with portal hypertension due to coexistent chronic liver disease.

34. Diagnosis Functional tests Imaging

35. Functional tests fecal elastase 1 level is the preferred noninvasive study to diagnose pancreatic exocrine insufficiency Normal - > 200 μg /g feces mild to moderate 100 - 200 μg /g severe pancreatic exocrine insufficiency< 100 μg /g Lipase and amylase are of minimal diagnostic value

36. Imaging Test of choice previously - ERCP Test of choice now - CECT CT has specificity of 85% to 100% for the diagnosis of chronic pancreatitis dilated pancreatic duct (68%), parenchymal atrophy (54%), and pancreatic calcifications (50%). Other findings include peripancreatic fluid, focal pancreatic enlargement, biliary duct dilation, and irregular pancreatic parenchyma contour

37. CECT

38. CECT

39. Imaging MRI is a reliable alternative MRCP with secretin injection - particularly useful - intraductal strictures and pancreatic duct disruption.

40. MRCP

41. Imaging role of ERCP ERCP was historically considered the “gold standard” for the diagnosis of chronic pancreatitis Indications include patients for whom CT and MRCP, are contraindicated/failed to corroborate the diagnosis Therapeutic modality - pancreatic duct complications amenable to endoscopic therapy, such as stricture, stone, pseudocysts , and biliary stenosis

42. Imaging - EUS EUS has emerged during the past 25 years as the most accurate technique to diagnose - in the early stages . Rosemont criteria – to diagnose chronic pancreatitis Features - Hyperechoic foci with postacoustic shadowing , Honeycombing lobularity Main pancreatic duct calculi , Main pancreatic duct dilation , Dilated side branches

43. Imaging - EUS

44. Management Abdominal pain Pancreatic insufficiency - steatorrhea

45. Pain management most debilitating symptom of chronic pancreatitis, as well as the one most often requiring medical care Identify associated conditions for which specific therapy exists – pseudocysts , duodenal obstruction, carcinoma

46. Pain – Medical management Some pts’ pain may be managed with acetaminophen; NSAIDs should be avoided. Pain management clinics should start with non narcotic analgesics Mostly they fail , it is useful to begin with lower potency opioid agents like tramadol . gradually increase the dosage , while focusing the patient on the goal of control of pain to an acceptable level rather than complete relief of pain

47. Pain – Medical management The risk of opiate addiction is estimated to be 10% to 30% - BUT Pain relief is the first priority Adjuncts - Tricyclic antidepressants , SSRI ,SNRI - modulating central pain perception , potentiate narcotics Gabapentoids - gabapentin & pregabalin

48. Pain management Cessation of alcohol and smoking : Most studies, have documented an apparent decrease in pain or painful relapses in patients who stop drinking alcohol

49. Pain management Anti oxidants : As such there is no clear evidence to support the use of these in pain management…. But in a large study conducted in india – tropical pancreatitis – there is improvement in pain and other symptoms Not found useful in elderly pts with chr.pancreatitis

50. Pain management Pancreatic Enzyme Therapy : Proteases supplementation to duodenum / proximal jejunum Reduce CCK release by destroying an intestinal CCK-releasing factor Octreotide – reduces circulating CCK levels

51. Endoscopic management goal of endoscopic therapy is to improve drainage of the pancreatic duct by relieving ductal obstruction . limited to a subgroup of patients with amenable pancreatic ductal anatomy ( single dominant stricture or an obstructing stone in the head of the pancreas )

52. Pain management Stent placement and sphincterotomy : stenosis of the sphincter has produced obstructive chronic pancreatitis complications are clogging of stents ( producing recurrent pain, attacks of acute pancreatitis, or pancreatic sepsis ), stent migration (which may require surgical extraction) and ductal perforation

53. Pain management ESWL : removal of large or impacted stones requires lithotripsy A survey from Japan in 555 patients reported complete stone clearance in 73% of patients.308 Pain improvement or relief is seen in about 75% to 90% of patients who undergo this type of therapy. there is some other effect on pancreatic pain separate from the ability to fragment pancreatic stones.

54. Pain management – surgery surgical treatment of CP is based on two main concepts : Resection of tissue : nondilated pancreatic ducts, pancreatic head enlargement, or if a pancreatic carcinoma is suspected Drainage & preservation of tissue : to prevent further loss of pancreatic function

55. Indications Intractable pain Symptomatic local complications Unsuccessful endoscopic management Suspicion of malignancy

56. Drainage / Decompression procedures Duval described using distal pancreatectomy and splenectomy with an end-to-end pancreaticojejunostomy between the cut end of the body or tall of the pancreas and a Roux-en-Y limb of jejunum to decompress the pancreatic duct .

57. Drainage - Puestow and Gillesby . ' Ihey modified Duval's procedure longitudinal opening along the main pancreatic duct through the tail and body of the pancreas and then invaginating the distal gland into a Roux-en-Y limb of jejunum

58. Longitudinal pancreaticojejunostomy Partington and Rochelle described the side-to-side longitudinal pancreaticojejunostomy that is currently referred to as the modified Puestow procedure . Remains as a standard approach to pancreatic ductal decompression best applied to patients with parenchymal disease and pancreatic ductal dilatation diffusely involving the pancreatic head. neck. body , and tail of the gland

59. Longitudinal pancreaticojejunostomy Minimal diameter of pancreatic duct should be >7 mm Should not be any mass in the pancreatic tissue Omitted splenectomy , distal pancreatectomy

60. Longitudinal pancreaticojejunostomy

61. Longitudinal pancreaticojejunostomy

62. LPJ – RESULTS 75–80% of patients with diffusely dilated main pancreatic ducts (>7 mm) and no dominant inflammatory mass, have achieved durable pain relief over 5–10 years of followup morbidity is low because no pancreatic parenchyma is removed, endocrine and exocrine functions are generally preserved

63. Resection procedures patients with focal disease largely confined to the head of the pancreas without duct dilation - pancreaticoduodenectomy [ PD] resection of the head of the pancreas with the distal CBD, distal stomach, duodenum, proximal jejunum

64. Resection procedures Beger introduced duodenum-preserving pancreatic head resection (DPPHR ) division of the neck of pancreas and removal of the head of the pancreas , leaving a small rim of pancreatic tissue along the duodenum.

65. Hybrid procedures - FREY procedure Frey introduced a procedure that combines duodenum-sparing resection of the pancreatic head, without formal division of the neck of the pancreas , combined with longitudinal pancreaticojejunostomy of the dorsal duct .

66. Hybrid procedures - FREY procedure

67. TOTAL PANCREATECTOMY WITH ISLET AUTOTRANSPLANTATION small duct disease diffuse parenchymal inflammation, hereditary syndromes, failures of prior pancreatic operations Complete or near complete pain relief in about 75% of patients , with 60% to 70% achieving narcotic independence

68. Nerve blocks and Neurolysis The celiac plexus transmits visceral afferent impulses from the pancreas The greater, lesser , and least splanchnic nerves travel from the celiac plexus and then pass through the diaphragm to reach the spinal cord .

69. Nerve blocks and Neurolysis Celiac plexus block (usually using a combination of a glucocorticoid and a long-acting local anesthetic like bupivacaine ) celiac plexus neurolysis (using an injection of absolute alcohol) can be administered by CT- or EUS-guided techniques These are used in pancreatic carcinoma

70. splanchnicectomy block central perception of nociceptive inputs. involves sectioning the greater splanchnic nerve on 1 or both sides using thoracoscopy 50 – 75 % will get pain releif The multiple spinal levels that receive input from the splanchnic nerves and the variation in the number of splanchnic roots , makes complete neurotomy difficult

71. Summary Benign inflammatory process and fibrosing disorder characterized by irreversible morphologic changes, Progressive and permanent loss of exocrine and endocrine function Alcohol consumption is the most common cause Pain is the most common symptom CECT is 1 st investigation of choice and best being EUS

72. Summary Treatment Local inflammation - Pharmacotherapy ( pancreatic enzymes,analgesics,narcotics ) Ductal hypertension - Decompression ( Puestow , endoscopic stenting ) Organ hypertension - Resection( Whipple,Frey ) Retroperitoneal - Neuroablation (celiac block, damage splanchnicectomy )

73. Thank you