Case Presentation

Joseph M Brandel, MDKings County Hospital CenterGeneral Surgical Service

May 14, 2004

Management of Pancreatic Necrosis

Definition

Lack of enhancement of the gland with liquefaction and loss of normal glandular texture of a portion or the entire pancreatic gland Severe injury with occlusions and thrombosis of the pancreatic microcirculationDoes not necessarily imply infection

History1882 – W.A. Balser postulates the presence of fatty necrosis in acute pancreatitis

Ueber Fettenneckrose, eine zuweilentödliche Krankheit des Menschen

1889 – R.H. Fitz suggests that extent of necrosis is sole determinant of survival

Argues against surgical interventionN. Senn vigorously disputes this conclusion

A century of controversy is born

EmbryologyDevelops from dorsal and ventral pancreatic buds that arise from the caudal part of the foregut

Dorsal bud appears during 4th week opposite the hepatic diverticulumVentral bud appears during the 5th

weekDuodenum rotates clockwise, carrying ventral bud alongFusion occurs during 7th weekAcinar and islet cells arise from foregut endoderm

EmbryologyDevelops from dorsal and ventral pancreatic buds that arise from the caudal part of the foregut

Dorsal bud appears during 4th week opposite the hepatic diverticulumVentral bud appears during the 5th

weekDuodenum rotates clockwise, carrying ventral bud alongFusion occurs during 7th weekAcinar and islet cells arise from foregut endoderm

Anatomy

Soft, oblong gland, 12-15 cm long, lying transversely in the retroperitoneal space Lies at L2/L3 levelDivided into head, body, and tailStomach anteriorly, duodenum to the right, spleen to the leftMain pancreatic duct (of Wirsung) has 20-30 lobular tributaries; in 10% the accessory duct (of Santorini) serves as the main route of pancreatic secretion

AnatomyBlood supply

Derived from celiac trunk and superior mesenteric arteryHead supplied by superior and inferior pancreaticoduodenalarteriesBody and tail supplied by transverse pancreatic artery

Statistics

185,000 new cases of acute pancreatitis per year in the US1

Alcohol is frequently said to be a close second to gallstones as an etiologic factorNecrosis present in 20 to 30 percent of casesAssociated with morbidity of 82% and mortality of 23%

1 Baron T, Morgan D. Acute Necrotizing Pancreatitis. NEJM. 1999 May 6;340(18):1412-17

Etiology: Alcohol

Pancreatitis is a consequence of chronic alcohol abuse; usually 6 to 10 yearsDaily consumption averages 100-150 g/day; 10% of heavy drinkers develop pancreatitisAssociated with HLA antigen types B40, Aw23, Aw24 and B13, blood groups O and LeMay cause spasm or inflammation of sphincter of OddiMay decrease solubility of intraductal proteins, promoting stone formationDecrease in pancreatic blood flow and alterations of lipid metabolism may contribute as well

Sakorafas GH, Tsiotou AG. Etiology and pathogenesis of acute pancreatitis. J Clin Gastroenterology. 30(4):343-56

Etiology: Alcohol

Both oxidative and nonoxidativemetabolism of ethanol occurs in pancreatic acinar cellsAcetaldehyde directly toxic to pancreasAlso inhibits secretionAlters redox state of cellIncreased oxidative stress

Wilson JS, Apte MV. Role of alcohol metabolism in alcoholic pancreatitis. Pancreas. 27(4):311-315

Etiology: Alcohol

FAEEs shown to induce pancreatic injury in vivo and in vitroActivate trypsinogenDestabilize lysosomesBoth acetaldehyde and FAEEs affect cytokine expressionSignaling molecules may provide therapeutic target

Prognostic indicatorsRanson’s criteria:

As defined by Ranson1, <3 positive signs predicted mortality of 0.9% and >6 positive signs predicted mortality of 100%More useful at extremes of severityBased on alcoholic pancreatitis; relevance to gallstone pancreatitis questionable2

Only allows for prediction after 48 hours

Glasgow criteria:No better3

1 Ranson JHC, Rifkind KM, et al. Prognostic signs and the role of operative management in acute pancreatitis. Surg Gynaecol Obstet 1974;139:69-812 Agarwal N, Pitchumoni CS. Assessment of severity in acute pancreatitis. Am J Gastroenterol 1991;86:1385-913 Corfield AP, Williamson RCN, et al. Predicition of severity in acute pancreatitis: prospective comparison of three prognostic indices. Lancet 1985:2:403-07

Present on Admission: Age greater than 55 years WBC greater than 16,000/ul Blood glucose greater than 200 mg/dl Serum LDH greater than 350 I.U./L SGOT (AST) greater than 250 I.U./LDeveloping During the First 48 Hours: Hematocrit fall greater than 10% BUN increase greater than 8 mg/dl Serum calcium less than 8 mg/dl Arterial oxygen saturation less than 60 mm Hg Base deficit greater than 4 meq/L Estimated fluid sequestration greater than 6 L

Prognostic indicators

APACHE-II, APACHE-O:Can be calculated immediately and daily thereafterPredicts 68% of severe attacks on admission vs. 34% by clinical assessmentAs good as Ranson and Glasgow after 48 hoursMay be the scoring system of choice

Triester SL, Kowdley KV. Prognostic factors in acute pancreatits. J Clin Gastroenterol 2002;34(2):167-76

Prognostic indicators

CT Severity IndexBased on extent of necrosisHigh correlation with morbidity and mortalityCannot distinguish between sterile and infected necrosisIV contrast may have deleterious effects on pancreatic microcirculation

Triester SL, Kowdley KV. Prognostic factors in acute pancreatits. J Clin Gastroenterol 2002;34(2):167-76

Medical Management

Critical careProphylactic antibiotics?

Infections occur in 30-40% of patients in who have over >30% necrosis1

Infectious complications account for 80% of deaths from pancreatitisBacterial translocation from gut implicated; enteric Gram negative organisms most frequently isolated2

1 Beger HG, Rau B, et al. Natural course of acute pancreatitis. World J Surg 1997;21:130-52 Ammori BJ. Role of the gut in the course of severe acute pancreatitis. Pancreas 2003;26:122-9

Medical management

10011Combination1996Delcenserie et al.

06813Ofloxacin1997Schwartz et al.

20713Control

111930Cefuroxime1995Sainio et al.

7131230Control

37412Control

182052Control

11950SGD1995Luiten et al.

3161033Control

36541Imipenem1993Pederzoli et al.

DeathSepsisPancreatic infection

nAntibiotic used

YearReference

Yousaf M, McCallion K, Diamond T. Management of severe acute pancreatitis. Br J Surg 2003;90:407-20

Operative Indications

Infected pancreatic necrosis is considered universally fatal without intervention1

Aggressive debridement on the basis of pancreatic necrosis alone was being advocated into the 1980s2

In 1991 Bradley and Allen3 established nonoperativemanagement of sterile necrosis as preferred option

Studied 194 consecutive patients with acute pancreatitis. 38 (20%) developed pancreatic necrosis. Of those, all 11 in whom the necrosis remained sterile were treated successfully without surgery

1 Banks PA. Infected necrosis: morbidity and therapeutic consequences. Hepatogastroenterology 1991;38:116-92 Rattner DW, Warshaw AL. Surgical intervention in acute pancreatitis. Crit Care Med 1988;16(1):89-953 Bradley III EL, Allen KA. Prospective longitudinal study of observation vs surgical intervention in the management of necrotizing pancreatitis. Am J Surg 1991;161:19-24

Operative Indications

Intractability?Persistent systemic illness (>4 weeks) is frequently cited as an indication for debridement of sterile necrosis1,2

Not a universally accepted indication3

1 Rau B, Pralle U, et al. Management of sterile necrosis in instances of severe acute pancreatitis. J Am Coll Surg1995;181:279-882 Rattner DW, Legermate DA, et al. Early surgical debridement of symptomatic pancreatic necrosis is beneficial irrespective of infection. Am J Surg 1992;163:105-10 3 Bradley III EL. Surgical indications and techniques in necrotizing pancreatitis. In: Bradley III EL, ed. Acute pancreatitis: diagnosis and therapy. New York: Raven Press, 1994:105-17

Operative Indications

Timing of surgery still debatedTrend toward delayed operation

Mier et al. randomized 41 patients to either early (48 to 72 hours) or late (>12 days) necrosectomy. 58% mortality in early group vs. 27% mortality in late groupBenefits of delayed surgery attributed to better demarcation between viable and nonviable tissue

Mier J, Leon EL, et al. Early versus late necrosectomy in severe necrotizing pancreatitis. Am J Surg 1997;173:71-5

Operative management: Evolution

Formal resection was standard treatment into the 1980s

Did not abort necrotic processExcessive removal of healthy tissueAbandoned due to high morbidity and mortality1

Nordback IH, Auvinen OA. Long-term results after pancreas resection for acute necrotizing pancreatitis. Br J Surg1985;72:687-9

Operative management: Evolution

Necrosectomy is the current standard of care

Removal of devitalized pancreatic parenchyma and retroperitoneal fatConventional: debridementwith Penrose drain1

Modifications include continuous irrigation, mandatory re-exploration, and laparostomy2

1 Altmeyer WA, Alexander JW. Pancreatic abscess: a study of 32 cases. Arch Surg 1963;87:80-892 Davidson ED, Bradley II EL. ‘Marsupialization’ in the treatment of pancreatic abscess. Surgery 1981;89:252-6

Interventional RadiologyRole in diagnosis clearly established

Diagnosis of pancreatic infection almost always requires tissue sample

Therapeutic role limitedPercutaneous drainage of solid necrotic material ineffective; Liquefied necrosis more amenable

Freeny et al.: Management of 34 patients with infected necrosis; 47% cured by this modality alone1

Echenique et al.: 20 patients with solid infected necrosis cured by catheter-based procedures. Mean 17 debridements per patient2

Very labor intensive, requiring multiple CT scans, catheter exchanges, and bedside visits by the interventionalist

1 Freeny PC, Hauptmann E, et al. Percutaneous CT-guided catheter drainage of infected acute necrotizing pancreatitis: techniques and results. Am J Roentgenol 1998;170:969-752 Echenique AM, Sleeman D, et al. Percutaneous catheter-directed debridement of infected pancreatic necrosis: results in 20 patients. J Vasc Interv Radiol 1998;9:565-71

Laparoscopy

Open necrosectomy associated with incisional hernia rate of 50% and enteric fistula rate of 20%Postulated advantages of laparoscopic approach are decreased recovery time, reduced patient pain, shorter ICU stay and shorter overall hospital stay

Gagner reported successful treatment of 6/8 patients with transperitoneal laparoscopy1

Retroperitoneal approaches, often in conjunction with percutaneous catheter placement, have been described as well2

Feasibility has been demonstrated; safety and efficacy have not1 Gagner M. Laparoscopic treatment of acute necrotizing pancreatitis. Semin Laparosc Surg 1996;3:21-282 Kelogg TA, Horvath KD. Minimal-access approaches to complications of acute pancreatitis and benign neoplasmsof the pancreas. Surg Endosc 200;17:1692-1704

Conclusions

Recognition of patients with pancreatitis who have or are at high risk of developing necrosis is of paramount importanceDetermining whether pancreatic necrosis is complicated by infection is pivotalThe subset of patients with infected necrosis is at high risk for morbidity and mortality; surgical debridement is the only established modality available to ameliorate the course of illness