Current Management Acute Pancreatitis, Clancy,

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Vol. 9, No. 32005 Current Management of Acute Pancreatitis 441

Clinical scoring systems specific for pancreatitis,such as the Ranson12 and Glasgow13 systems, havebeen shown to predict outcomes in groups of patientswith acute pancreatitis but require 48 hours fromadmission for full assessment. Furthermore, althoughhigher scores suggest poorer outcomes, these scoring

systems have not been adequately reassessed to reflectthe substantial improvements in critical care sincetheir introduction more than two decades ago.14

The Acute Physiology And Chronic Health Evalua-tion (APACHE II) score, although not specific forpancreatitis and somewhat more cumbersome, is asaccurate at 24 hours as are other systems at 48hours and therefore is thought to be the optimalscoring system to assess disease severity.9 Unlikeother systems, the APACHE II score may be continu-ously recalculated through the course of the disease.APACHE II scores have also been identified as an

independent predictor of outcome after pancreaticdebridement.15The newer APACHE III system usesan additional five physiologic variables to improveaccuracy, although the newer system may be lessuseful than the APACHE II score in distinguishingmild from severe pancreatitis.16A recent modificationof the APACHE II system, which includes a clinicalassessment of obesity (APACHE-O score), has beensuggested to further improve predictive accuracy,with a positive predictive value of 74%.17

In addition to multiple-factor scoring systems, sev-eral isolated indicators of prognosis have been sug-gested. Brown et al.18 and Lankisch et al.19 haveshown that hemoconcentration predicts necrotizingpancreatitis and organ failure. A number of biologicalmarkers have been studied as prognostic markers inboth laboratory and clinical settings; none have yetgained widespread clinical applicability. C-reactiveprotein (CRP) is readily available and rises with dis-ease severity; however, it is useful to identify severedisease only 48 hours after the onset of symptoms.20

Inflammatory mediators such as interleukin (IL)-8and IL-6 show promise as early indicators of severedisease but await general availability and furtherclinical validation.21 Assays for other markers of in-

flammation, including tumor necrosis factorsolublereceptors and polymorphonuclear elastase, await clin-ical validation and the availability of reproducibleassays before their use as prognostic markers inacute pancreatitis. Several other markers of inflam-mation have been investigated in this regard, includ-ing serum procalcitonin, soluble IL-2 receptors, andsoluble E-selectin,22 although clinical usefulness ofthese markers awaits further investigation.

A growing body of literature suggests that assaysfor trypsinogen activation peptide (TAP) may be auseful marker of disease severity. TAP, released with

activation of trypsinogen to trypsin, is known to cor-relate with severity of pancreatitis. However, the mol-ecule is present in low concentrations in urine and iscleared rapidly from plasma. Recent reports of highsensitivity and specificity of elevated urinary TAPin severe pancreatitis23,24 are promising; similarly, a

recent report of plasma TAP levels suggested thatsevere acute pancreatitis could be recognized withsensitivity and specificity of 70% and 78%, respec-tively, using a plasma assay.25 Reliable TAP assaysmay prove to be clinically useful as an indicator ofdisease severity.

The computed tomography (CT) scan is an im-portant adjunct in determining disease severity inacute pancreatitis.26 CT findings in pancreatitisinclude enlargement of the pancreas with loss of peri-pancreatic fat planes, areas of decreased density, andoccasionally the presence of fluid collections (Fig. 1).

The presence of pancreatic inflammation and peri-pancreatic fluid collections has been incorporatedinto grading systems such as the Balthazar system,and CT findings have thereby been correlated withmorbidity and mortality.27,28The use of dynamic con-trast-enhanced CT is perhaps most useful in its abilityto demonstrate pancreatic necrosis. Nonenhancedpancreas will show CT attenuation numbers of 3050 Hounsfield units (HU) that increase by more

Fig. 1. Contrast-enhanced abdominal computed tomographyscan in a 47-year-old man with acute pancreatitis. Relevantfindings include significant fat stranding of the peripancreatictissue, with a fluid collection at the tail of the pancreas measur-ing approximately 4 cm 4 cm. Pancreatic parenchyma en-hances with intravenous contrast, with no evidence ofpancreatic necrosis.


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Journal ofGastrointestinal Surgery442 Clancy et al.

Fig. 2. Contrast-enhanced abdominal computed tomographyscan in the 47-year-old man shown in Fig. 1 with a secondepisode of acute pancreatitis. Scan shows stranding of peripan-creatic fat, consistent with acute pancreatitis. Most notable isthe near-complete absence of pancreatic enhancement, diag-nostic of pancreatic necrosis.

than 50 HU with intravenous contrast, but a decreasein or lack of enhancement ofpancreatic parenchyma

correlateswith necrosis (Fig.2).Recognizedcriteriatodiagnose necrosis include nonenhancement of morethan 30% of the pancreatic parenchyma or an area ofgreater than 3 cm without enhancement.29 Sensitivityand specificity increase with degree of nonenhance-ment, and degree of complications has been shownto correlate with degree of nonenhancement.28

Contrast-enhanced CT scan may be contraindicatedin the presence of renal impairment or a history ofallergic reaction to intravenous contrast; althoughnonenhanced CT provides important information,recent data support the use of magnetic resonance

imaging (MRI) as an alternative. MRI and CThave been shown to have comparable sensitivity andspecificity for severe acute pancreatitis30; whetherMRI is practical for most critically ill patients remainsto be determined.

The timing of imaging studies remains an issue ofsome discussion. Early scans may not identify devel-oping necrosis until such areas are better demarcated,often 23 days after the initial clinical onset. No datasupport the use of CT to diagnose necrosis or topredict severity within the first 24 hours of illness.Limited and contradictory experimental evidence

has suggested that intravenous contrast might exacer-bate early pancreatic necrosis,31 although clinical evi-dence to support this phenomenon in humans islacking. Sensitivity for the diagnosis of pancreaticnecrosis approaches 100% after 4 days from diagno-sis.9 In general, patients with clinical and biochemical

features of acute pancreatitis who do not improvewith conservative management should undergo anabdominal CT scan with oral and intravenouscontrast. Follow-up scans may be obtained with anysigns of clinical deterioration.

Although clinicians in recent years have adoptedincreasingly conservative trends in the managementof sterile pancreatic necrosis, infection remains anabsolute indication for intervention.1 The early andaccurate diagnosis of infected pancreatic necrosis istherefore desirable. Clinical and laboratory featuresof infected pancreatic necrosis, such as significant

leukocytosis and fever, are also seen in severe sterilenecrosis. Radiographic evidence of infection, or em-physematous pancreatitis, is uncommon. The abilityto use image-guided percutaneous aspiration to diag-nose infection in patients with pancreatic necrosiswho are not improving clinically has therefore beena major advance (Fig. 3). The sensitivity and specific-ity for detection of infection are reported as 96.2%and 99.4%, respectively, with a positive predictive

Fig. 3. Computed tomography (CT)-guided percutaneous fineneedle aspiration of the pancreatic tail. The aspiration areahad previously been identified as necrotic in the contrast-enhanced CT scan shown in Fig. 2. Gram stain and cultureswere negative for organisms, consistent with sterile pancre-atic necrosis.


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value of 99.5% and negative predictive value of95.3%.32 Samples are sent for aerobic, anaerobic, andfungal culture, although Gram stain of the aspirateis positive in the majority of cases with infection.The interval from initial presentation to infection isvariable, and pancreatic necrosis is variable, and in-

creases up to 3 weeks. For this reason, repeat CT-guided aspirations are often necessary. In a series atour institution with fine needle aspirations (FNAs)demonstrating infection, the first aspirate was positivein 17 of 30 patients (57%); 7 patients (23%) requiredtwo procedures and 6 patients (20%) required threeor more aspirations to demonstrate infection.33

PRINCIPLES OF MANAGEMENTResuscitation and Monitoring

Medical therapy for acute pancreatitis has become

increasingly standardized in recent years.3,3436 Analgorithm for the diagnosis and management of acutepancreatitis is suggested in Fig. 4. A cornerstone ofinitial management is aggressive fluid resuscitationto replenish the often massive third-space losses.Intravenous fluids at rates of greater than 200 ml/hrare necessary to restore and maintain intravascularvolume, and close monitoring of respiratory, cardio-vascular, and renal function is required to detect andtreat complications from hypovolemia. Inadequatefluid resuscitation not only predisposes to systemiccomplications, particularly acute renal insufficiency,

but also has recently been shown to pose a significantrisk for further pancreatic injury. Brown et al.37 haveshown that although aggressive fluid resuscitationdoes not necessarily prevent the progression topancreatic necrosis, patients with inadequate resusci-tation have an increased risk of developing necrosis.Monitoring is tailored to disease severity. All pa-tients require close assessment of fluid balance includ-ing the use of a Foley catheter. Close monitoring forrespiratory compromise and electrolyte imbalance isimportant in all, and any patient with severe diseaseshould be admitted to an intensive care unit withthe capacity for continuous blood pressure andoxygen saturation monitoring. Intravenous narcoticsare often essential for pain control in these pa-tients. No data support the use of nasogastric drainageto reduce the severity of pancreatitis, although it maybe useful in treating ileus and preventing aspirationpneumonia.

Nutritional Support

Classic teaching in the management in pancreatitishas included the limitation of enteral feeding, theo-retically to avoid stimulation of pancreatic exocrine

function and thereby avoid further pancreatic injuryfrom release of proteolytic enzymes. Brief periodswithout oral intake may be expected in very mildcases of pancreatitis, and a full diet is often possiblein several days withthe resolution of pain. Severe casesmay have a prolonged course, hypercatabolic state,

and ileus, which has led to a general use of parenteralnutrition in these patients.38 In recent years, increas-ing evidence has accumulated to suggest that enteralnutrition may be feasible and safe even for cases ofsevere pancreatitis39 (Table 1). In addition to avoidingthe cost of and catheter-related complications associ-ated with total parenteral nutrition (TPN), enteralnutrition may avoid the alterations to intestinal bar-rier function and altered intestinal permeability seenwith TPN.40 For instance, a small trial from 1997randomized 38 patients with severe pancreatitis toTPN versus nasojejunal feeding.41 In this cohort, en-

terally fed patients had significantly fewer septic andtotal complications. McClave et al.42 randomized 30patients in a similar fashion and demonstrated onlyatrendtowardfewercomplicationsintheenterallyfedgroup. The one significant advantage of enteral nutri-tion was cost, which was four times greater in theTPN group. Windsor et al.43 demonstrated that pan-creatitis patients randomized to enteral nutrition hadsignificant improvement in CRP and APACHE IIscores. Recently, a larger study from China44 random-ized 96 patients with severe pancreatitis to TPNversus nasojejunal feeding. Measures of inflammationincluding CRP and IL-6 decreased earlier withenteral nutrition, as did APACHE II scores. Further-more, mucosal permeability was improved, as inferredby urine endotoxin levels. Others have suggested thatthe addition of Lactobacillus preparations to enteralnutrition formulas may have a role in decreasing in-fectious complications in pancreatitis.45 The above-mentioned studies all involve nasojejunal feeding,although others have investigated the counterintu-itive use of nasogastric feeding in pancreatitis. Inves-tigators from Glasgow46 have recently shown in anonrandomized cohort with severe pancreatitis thatnasogastric feeding is well tolerated in most patients.

Whether this method is feasible and provides suffi-cient caloric support deserves further investigation.

Although a recent systematic review of the litera-ture has not concluded that there are sufficient datato definitively recommend enteral nutrition in acutepancreatitis,47 studies continue to accumulate demon-strating its safety and feasibility. TPN will continueto have an important role in severe pancreatitis, par-ticularly in cases with prolonged ileus. However, earlyenteral nutrition should be considered for patientswho will not resume oral intake early in the courseof their disease.


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Fig. 4. Management algorithm for acute pancreatitis. APACHE II Acute Physiology And ChronicHealth Evaluation, CRP C-reactive protein, ICU intensive care unit, NPO nothing by mouth,NGT nasogastric tube, ERCP endoscopic retrograde cholangiopancreatography, CT computedtomography, TPN total parenteral nutrition, AP acute pancreatitis, FNA fine needle aspiration,WBCwhite blood cells.

The Role of Endoscopic RetrogradeCholangiopancreatography

Gallstones are increasingly recognized as the pri-mary cause of most cases of acute pancreatitis.48 The

role of endoscopic retrograde cholangiopancreatog-raphy (ERCP) as a diagnostic and potentially thera-peutic modality in acute pancreatitis has been thesubject of some debate. Although early ERCP is notused in mild cases, its role in acute biliary pancreatitis


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Table1.

Controlledtrialsofnu

tritionalsupportinpatientswitha

cutepancreatitis

Author

InclusionCriteria

N

Design

Outcome

Find

ings

Saxetal.9

2(1987)

Acutepancreatitis

54

Earlytotalparenteralnutrition

Daystooraldiet,lengthof

NoadvantagetoTP

N

versusnonutritionalsupport

stay(LOS

),complications

McClaveetal.4

2(1997)

Acutepancreatitis

32

Entera

lversusparenteral

Daystooraldiet,LOS,

Betteroutcomewith

enteralgroup;

nutrition

infectionrate,mortality,

costisonlysignifi

cantdifference

cost

(lesswithenteral)

Kalfarentzosetal.4

1(1997)Glasgo

wComaScalescore3,38

Entera

lversusparenteral

Complicatio

ns,LOS,cost

Fewersepticandtotalcomplications

APA

CHEIIscore8,

nutrition

withenteralnutrition,cost

C-re

activeprotein

significantlylessw

ithenteral

(CRP),120mg/L,or

nutrition

gradeD/EBalthazarscore

Windsoretal.4

3(1998)

Serum

amylase1000U/L

34

Entera

lversusparenteral

APACHEIIscore,CRP,

Significantdecrease

inAPACHEII

nutrition

sepsis,organdysfunction,

scoreandCRPin

enteralgroup

LOS,mortality

onlyat7days;sepsis,organ

dysfunction,LOS,mortalitywith

nonsignificanttrendtoimprovement

withenteralnutrition

deBeauxetal.9

3(1998)

Glasgo

wComaScale

14

Parenteralnutrition

Changeininflammatory

Nonsignificanttrendtoimproved

score3

conv

entionalversus

mediators

lymphocyteprolif

erationand

glutamineenhanced

interleukin8releaseinglutamine

group

ModifiedfromLoboetal.3

9

with biliary obstruction or cholangitis is not disputed.More controversial is the utilization of early ERCPand papillotomy in acute biliary pancreatitis withoutobstruction. Both Neoptolemos et al.49 andFanetal.50

demonstrated a significant reduction in morbiditywith nonsignificant trends to improved mortality

when patients with acute pancreatitis are randomizedto early ERCP. These studies were criticized for theinclusion of patients with obstruction and cholangitisin the cohort, possibly accounting for the observedbenefit from intervention. A more recent multicenterrandomized study by Folsch et al.,51 which excludedpatients with known biliary sepsis or obstruction,demonstrated increased complications and mortalityin the ERCP group. It was therefore suggested thatearly ERCP might be harmful in the absence of ongo-ing obstruction. Although these findings have beensubsequently called into question given the small

number of patients per center,52 it is generallythought that there is insufficient evidence to recom-mend ERCP in acute biliary pancreatitis in the ab-sence of biliary obstruction or infection. Recentadvances in diagnostic radiology have provided clini-cians with magnetic resonance cholangiopancreatog-raphy (MRCP) as an alternative to ERCP. AlthoughMRCP does not allow therapeutic maneuvers to clearidentified stones, it may play an important diagnosticrole when ERCP cannot be performed.53 As men-tioned previously, the use of MRI techniques posesunique challenges in the critically ill patient, includ-

ing the need for prolonged scan times and compatiblenonmetallic equipment for ventilators and intra-venous fluid administration. As technology evolves,it is expected that MRI and MRCP will play an in-creased role in the diagnosis of pancreatitis andductal obstruction.

Antibiotics

The vast majority of deaths from pancreatitis occurfrom local and systemic infectious complications.Local infection occurs more commonly in patients

with increasing amounts of pancreatic necrosis andis more often seen late in the course of the disease. Inone study, 24% of patients operated on for pancreaticnecrosis had infection at 1 week, whereas 71% ofpatients were infected when exploration was per-formed at 3 weeks.54 Infection of necrotic pancreatictissue usually involves aerobic and anaerobic gastroin-testinal flora, and infections may be monomicrobialor polymicrobial. In a collected series of more than1,100 cases, the organisms involved were Escherichiacoli (35%), Klebsiella pneumoniae (24%), Enterococcus(24%), Staphylococcus(14%), andPseudomonas(11%).55


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Exposure to broad-spectrum antibiotics is demon-strated to alter the bacterial flora of pancreatic infec-tions, with a tendency to develop antibiotic-resistantbacterial infections and fungal infections.56,57 Still,the clear association of pancreatic infection with mor-tality has driven the widespread use of prophylactic

systemic antibiotics for pancreatic necrosis. The useof antibiotics to prevent or forestall pancreatic infec-tion has been widely investigated.58,59

Numerous animal studies have shown a benefitfrom early antibiotic administration with pancreati-tis,58 but this benefit has not been as consistentlydemonstrated in humans. Early clinical studies of pro-phylactic antibiotics in pancreatitis did not show abenefit, possibly due to inclusion of patients at lowrisk for infection or for the use of antibiotics withpoor pancreatic penetration. A significant investiga-tive effort has been put forth to characterize the

penetration ofvarious antibiotics into the pancreaticparenchyma.60 Still, the precise relation between anti-biotic levels in pancreatic tissue and efficacy in pre-venting or treating infection in necrotic pancreatictissue is unclear.

Several recent studies have addressed the use ofsystemic antibiotic prophylaxis in severe pancreatitis,with somewhat conflicting results (Table 2). Peder-zoli et al.61 randomized 74 patients with necrotizingpancreatitis to systemic imipenem or no antibiotics.While pancreatic infection was decreased with imi-penem (12% versus 30%), there was no difference inthe rate of multiorgan system failure, need for sur-gery, or overall mortality. Of note, antibiotic therapywas particularly useful with mild necrosis; no patientwith less than 50% necrosis developed septic compli-cations with imipenem compared with 29% in thecontrol group.

In contrast, Saino et al.62 showed a decrease ininfectious complications, operations, and mortalitywith the use of cefuroxime in a randomized fashionin patients with necrotizing alcoholic pancreatitis.However, the apparent mortality benefit was notassociated with any difference in local pancreatic in-fection. Further criticisms include a high incidence

ofantibioticuseatsomepointintherapyinthecontrolarm of the study. Another small randomized study63

with 26 patients showed a nonsignificant trend toimproved mortality with intravenous ofloxacin andmetronidazole for CT-confirmed pancreatic necrosis.Still others64 suggested no difference in mortality orthe development of infected pancreatic necrosis withthe use of ciprofloxacin and metronidazole, al-though this study was not limited to patients withCT-confirmed pancreatic necrosis.

The inconsistencies among these small trials mayresult from the relatively small number of patients

per study and the limited statistical power to detectsuch differences. In addition, there is considerableheterogeneity in patient selection (use of CT criteriafor necrosis, etiology of pancreatitis) and antimicrobi-als used. Other differences exist among the studiesin the nonantibiotic management of patients, particu-

larly with fluid resuscitation, enteral nutrition, timingof surgery, and other factors. Meta-analyses havebeen performed to address this question. In one, 65

early antibiotic use was associated with decreasedmortality from pancreatitis for patients with severepancreatitis receiving broad-spectrum antibiotics. Asecond meta-analysis looked at randomized, con-trolled, nonblinded studies of prophylactic antibioticsin necrotizing pancreatitis. A nonsignificant trendtoward decreased local infection was suggested withthe use of imipenem, cefuroxime, or ofloxacin. Sepsisand overall mortality were significantly lower with

antibiotic use, and the authors therefore supportedthe use of prophylactic antibiotics for all patients withacute necrotizing pancreatitis.66

Despite variations in institutional practices, a con-sensus is emerging that broad-spectrum antibioticsshould be initiated early in patients with necrotizingpancreatitis, particularly with signs of organ failureor systemic sepsis.67 The risks of superinfection withfungal or antibiotic-resistant organisms is well-recog-nized,68 and length of treatment is therefore typicallylimited. Although the optimal duration of antimicro-bial therapy has not been defined, the incidence ofpancreatic infection increases for approximately thefirst 3 weeks after diagnosis.69 A treatment course of14 weeks is therefore generally pursued, with manyauthors limiting treatment to 14 days.5 The role ofprophylactic antifungal therapy is also undefined, al-though mortality is high when fungal infection com-plicates the use of prophylactic antibiotics. Somegroups have therefore recommended fluconazole forall patients receiving antibiotic therapy for necrotiz-ing pancreatitis.57 A recent randomized trial of anti-fungal therapy in severe acute pancreatitis showed adefinite reduction in the incidence of fungal infectionwith the prophylactic use of the antifungal garlicin or

fluconazole.70 Given a relatively low incidence of sideeffects from fluconazole, this approach may be anappropriate adjunct to the prophylactic regimen.

Given the gastrointestinal origin of bacteria in in-fected pancreatic necrosis, pancreatic infection mighttheoretically be reduced through the reduction ofintestinal bacteria. Early laboratory evidence sug-gested that gut decontamination might decrease mor-tality in experimental pancreatitis, lending support tothe role of intestinal bacteria in pancreatic infection.71

Selective gut decontamination has been reported inonly one clinical study. Luiten et al.72 randomized


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Table 2. Controlled trials of antibiotic use in acute pancreatitis

Mortality rate (%)

Author Inclusion Criteria N Antibiotic regimen Controls Antibiotic Group

Pederzoli et al.61 (1993) Acute pancreatitis, necrosis on 74 Imipenem for 14 days 12 7 computed tomography (CT) scan

Sainio et al.62 (1995) CRP 120 mg/L, decreased 60 Cefuroxime for 14 days 23 3 pancreatic enhancement or until CRP normalized on CT

Luiten et al.72 (1995) Imrie score 3, Balthazar 102 Oral colistin, amphotericin, 35 22 CT grade D or E and norfloxacin until

clinical recovery, plus intravenous (IV) cefotaxime until gram- negative bacteria eliminatedfrom oral cavity

Delcenserie et al.94 (1996) Acute pancreatitis, 2 23 Ceftazidime, amikacin, and 25 9 fluid collections on CT metronidazole for 10 days

Schwarz et al.63 (1997) Acute pancreatitis with 26 Ofloxacin and metronidazole 15 0 pancreatic necrosis on CT for 10 days

Isenmann et al.64 (2004) Acute pancreatitis, 114 IV ciprofloxacin and metronidazole 5 7 CRP, 150 mg/L for 14 days if clinical or necrosis on CT improvement, or 21 days

Modified from Golub et al.65


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patients with severe acute pancreatitis to oral andrectal administration of nonabsorbable antibiotics.Mortality was decreased in the treatment group, pre-dominantly via a reduction in late mortality anddecrease in gram-negative pancreatic infection. How-ever, the short use of intravenous antibiotics in the

study may confound the results, and the effect of gutdecontamination alone is unclear. Definitive recom-mendations regarding the use of gut decontaminationawaits further studies.

Surgical Management

In the majority of patients with acute pancreatitis,the process is limited to parenchymal edema withoutnecrosis. In these patients, surgical therapy is largelylimited to the delayed treatment of local complica-tions, such as pseudocysts, and to the use of cholecys-

tectomy to prevent further illness. Between 10% and30% of patients develop severe illness, with pancreaticand peripancreatic necrosis, as well as the systemic in-flammatory response syndrome and considerable mor-bidity and mortality.2 This latter group of patientsmay require debridement or other aggressive in-tervention during the acute phase of the disease.Although an increasingly conservative surgical ap-proach has been adopted in recent years, the timingof debridement and the indications for debridementin patients with sterile necrosis remain controversial.

Patients with infected pancreatic necrosis accountfor the majority of the deaths from acute pancreatitis,and the absolute need for debridement is generallyaccepted. The mortality rate from necrotizing pan-creatitis has historically been reported to range from20% to 40%, although recent reports suggest thismay be reduced to less than 15% with appropriatemonitoring and intervention.4,33,73,74Mortality in in-fected pancreatic necrosis is virtually 100% withoutdebridement. Radiographic signs of pancreatic infec-tion such as emphysematous pancreatitis are seen inonly a minority of cases; CT-guided FNA is thereforetypically required to diagnose infection.

Historically, the presence of pancreatic necrosis

was considered sufficient justification for surgical de-bridement. Bradley and Allen54 questioned this prac-tice in 1991 with the publication of a small series of11 patients with sterile pancreatic necrosis managednonoperatively. Indications for surgery in patientswith sterile necrosis have continued to be refinedsince that time. Some authors have argued that pa-tients with severe disease benefit from debridementregardless of the status of infection.75 Considerableeffort has been made to identify criteria for debride-ment other than infection.76,77 Unfortunately, nonehave shown to be specific enough to use as a basis of

decision-making.78 Series using aggressive surgeryregardless of pancreatic infection continue to bereported,73,74 although most centers have increasinglymanaged sterile necrosis in a conservative manner. Aprospective study from Bern4 followed 86 patientswith necrotizing pancreatitis prospectively with a

conservative protocol, reporting a mortality rate of10% and the need for operation in the absenceof documented infection in only one patient. A retro-spective review of conservative management of sterilenecrosis was recently reported from Brigham andWomens Hospital.33 Of note, 59 patients did notdevelop infection and were managed conservativelywith a mortality of 11%. Thirty-four patients devel-oped infected necrosis requiring debridement ordrainage, and mortality in this group was 12%. Ofnote, when analyzing the patients who died, the au-thors were not able to find clinical or laboratory char-acteristics that would help prospectively identifypatients who might benefit from more aggressivemanagement. Overall, the results suggest that conser-vative strategies can be used in most patients withsterile necrosis with reasonable outcomes (Fig. 5).

Despite a general acceptance among most authorsof initial nonoperative management for sterile pan-creatic necrosis, some have emphasized the eventualneed to operate on patients who do not clinicallyimprove. Warshaw79 described a group of patientswith sterile necrosis who have persistent un-wellness, with continuing pain, malaise, and inabilityto eat. Isenmann et al.80 described other patients with

sterile necrosis but persistent organ failure for whomconservative treatment failed due to the severity oftheir systemic illness. Unfortunately, the precise indi-cations for and timing of surgery for this group ofpatients have not been precisely defined. Small non-randomized series suggest better outcomes with de-layed versus early debridement.73,81 The pathologiccorrelate of the pancreas later in the course of thedisease is what Baron et al.82 describe as organizedpancreatic necrosis: a process of maturation of theinflammatory tissue with improved demarcation fromhealthy pancreatic and peripancreatic tissue. In theabove-mentioned series of 99 patients with pancreatic

necrosis at the Brigham and Womens Hospital, 5patients underwent an operation for this indicationat a mean of 29 days (2334) after presentation. Thisgroup accounted for approximately one fifth of thepatients who had undergone a negative CT-guidedFNA.33 Fernandez-del Castillo and associates73 sug-gested that there is no added benefit in these patientsin waiting longer than 27 days from the onset ofillness. Such delayed procedures are an importantpart of a conservative management strategy that em-phasizes nonoperative management for most cases ofsterile necrosis and late operations whenever possible.


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Fig. 5. Management strategy in necrotizing pancreatitis. CT computed tomography; FNA fineneedle aspiration; LOS length of stay. Reproduced with permission from Ashley SW, Peres A, PierceEA, et al. Necrotizing pancreatitis: Contemporary analysis of 99 consecutive cases. Ann Surg 2001;234:572580.

A variety of techniques have been described forpancreatic debridement and drainage,73,74,83,84 all ofwhich involve open debridement followed by externaldrainage of some sort. Three general approaches in-clude the following: (1) open debridementwith abdom-inal closure and external drainage via closed suctionor Penrose drains, (2) debridement with placement ofseveral soft drains in the retroperitoneum for continu-ous lavage, or (3) aggressive debridement with openpacking and planned reexploration. The necrosec-tomy may be approached via the gastrocolic ligamentor through the transverse mesocolon. In general, anapproach tailored to the location of necrotic tissueon CT imaging may be most beneficial. Debridementis done primarily with blunt technique, attemptingto remove as much necrotic tissue as deemed safe.Formal pancreatic resection is not indicated in thissetting.

If debridement is adequate, multiple soft drainsare placed and the abdomen closed, with the under-standing that reexploration is required in more thanone third of patients for ongoing necrosis. If debride-ment is thought to be inadequate, postoperativeclosed high-volume lavage via large drains in the lesser

sac has been described with some success for residualnecrotic tissue.84,85 In other patients who have onlylimited debridement due to bleeding or with a clearneed for further debridement, open packing is appro-priate. This approach is associated with a high inci-dence of postoperative complications, especiallyenteric fistulas. In our recent series of 99 patientswith pancreatic necrosis,33 31 of 36 patients managedsurgically were adequately treated with closed drain-age. A conservative approach with delayed surgicalintervention may in fact facilitate a closed drainagetechnique.

Minimally Invasive Approaches

Traditional open surgical techniques remain thegold standard of therapy for patients who requiredebridement. In recent years, however, there has beena proliferation of reports suggesting that minimallyinvasive approaches may be of benefit in some cases ofnecrotizing pancreatitis. Percutaneous, endoscopic,and laparoscopic techniques have all been described.Solid pancreatic debris has traditionally been thoughtto be too thick for adequate evacuation with percuta-neous drains; still, at least one study has demonstrated

successful percutaneous management in infected pan-creatic necrosis. Freeny et al.86 successfully managed16 of 34 such patients with percutaneous methodsalone; in 9 others, percutaneous intervention was notthe sole means of therapy but allowed eventual opensurgical intervention to be delayed. The concept thatpercutaneous drainage of infected necrosis may delaythe need for early intervention, permitting surgeryonce the process has become more organized, is ap-pealing but needs further validation.

Other investigators have suggested endoscopictherapy for pancreatic necrosis and have recentlysummarized these results.87 Forty-four patients withpancreatic necrosis were treated for suspected or doc-umented infection or for intractable symptoms fromorganized necrosis, including nausea, pain, or earlysatiety. Endoscopic transmural drainage was success-ful in 31 (72%) of patients with pancreatic necro-sis, although 9 (29%) experienced recurrence and 16(37%) experienced complications. Transmural drain-agewasmoresuccessfulwithcentralnecrosisthanwithperipheral necrosis due to close proximityof the ne-crotic area to the gastric wall. Seifert et al.88 described


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a method of retroperitoneal endoscopy via transgas-tric fenestration. Direct visual access to retroperito-neal collections is thereby afforded to allow optimaldrainage. Few patients have been described using thismethod, and larger studies are necessary to validatethis approach. The above approaches were not always

performed for infected pancreatic necrosis. Of con-cern is the certainty that if sterile collections are ac-cessed via the gastrointestinal tract, these collectionssoon become contaminated.89 Inadequate drainagetherefore clearly has the ability to complicate a trou-blesome but not life-threatening collection.

A number of minimal access surgical techniqueshave been proposed to assist with management ofpancreatic necrosis. Gambiez et al.90 suggest using aretroperitoneal approach via dorsal lumbotomy anda 23-cm endoscope to explore and drain the peripan-creatic area; necrotic peripancreatic tissue could be

removed by blunt dissection and drains may be leftfor irrigation. This procedure was repeated at regular5-day intervals until the resolution of necrotic debris,with a mean of five procedures. Purported advan-tages include an avoidance of peritoneal contamina-tion, and subsequent laparotomy was required injust two patients for persistent collections. Overallmortality in 20 patients with infected pancreatic ne-crosis was 10%, which compares favorably with his-torical controls. Larger studies should help clarifywhether direct retroperitoneal endoscopy is feasiblein most patients. Laparoscopic techniques have also

been described for direct debridement in pancreaticnecrosis,91 although further study is indicated.

Summary

The treatment of mild pancreatitis has changedlittle in recent years, but advances in the managementof severe pancreatitis have been associated with sig-nificantly reduced morbidity and mortality. Improve-ments in the recognition of severe disease withscoring systems and serial CT scanning has allowedearly goal-directed therapy in appropriate patients.

Early aggressive resuscitation and invasive monitor-ing are standard, with an increased recognition ofthe role of prophylactic antibiotics and image-guidedFNA to diagnose infection. Although the need foraggressive intervention in infected pancreatic necro-sis remains unchanged, initial conservative manage-ment of most patients with sterile pancreatic necrosishas gained widespread acceptance. Some patientswith sterile necrosis may eventually require delayeddebridement either for persistent systemic illness orfailure to thrive, although accurate prospective identi-fication of these patients has not been possible. For

patients who need debridement, open surgical tech-niques remain the gold standard of management. Ad-vances in minimally invasive technology hold promiseas adjuncts to open procedures in the future, particu-larly as a means of delaying surgery until the necrosisbecomes more organized.

REFERENCES

1. Banks PA. Acute pancreatitis: Medical and surgical manage-ment. Am J Gastroenterol 1994;89:S78S85.

2. Beger HG, Rau B, Mayer J, Pralle U. Natural course of acutepancreatitis. World J Surg 1997;21:130135.

3. Yousaf M, McCallion K, Diamond T. Management of severeacute pancreatitis. Br J Surg 2003;90:407420.

4. Buchler MW, Gloor B, Muller CA, Friess H, Seiler CA,Uhl W. Acute necrotizing pancreatitis: Treatment strategyaccording to the status of infection. Ann Surg 2000;232:619626.

5. Clancy TE, Ashley SW. Current management of necrotizing

pancreatitis. Adv Surg 2002;36:103121.6. Kazmierczak SC, Catrou PG, Van Lente F. Diagnostic accu-

racy of pancreatic enzymes evaluated by use of multivariatedata analysis. Clin Chem 1993;39:19601965.

7. Sternby B, OBrien JF, Zinsmeister AR, DiMagno EP. Whatis the best biochemical test to diagnose acute pancreatitis? Aprospective clinical study. Mayo Clin Proc 1996;71:11381144.

8. Clavien PA, Robert J, Meyer P, et al. Acute pancreatitis andnormoamylasemia. Not an uncommon combination. AnnSurg 1989;210:614630.

9. Dervenis C, Johnson CD, Bassi C, et al. Diagnosis, objectiveassessment of severity, and management of acute pancreatitis.Santorini Consensus Conference. Int J Pancreatol 1999;25:195110.

10. Baron TH, Morgan DE. Acute necrotizing pancreatitis. NEngl J Med 1999;340:14121417.

11. Lerch MM, Hernandez CA, Adler G. Acute pancreatitis. NEngl J Med 1994;331:948949.

12. Ranson JH, Rifkind KM, Roses DF, Fink SD, Eng K, Spen-cer FC. Prognostic signs and the role of operative manage-ment in acute pancreatitis. Surg Gynecol Obstet 1974;139:6981.

13. Blamey SL, Imrie CW, ONeill J, Gilmour WH, Carter DC.Prognostic factors in acute pancreatitis. Gut 1984;25:13401346.

14. Eachempati SR, Hydo LJ, Barie PS. Severity scoring forprognostication in patients with severe acute pancreatitis:Comparative analysis of the Ranson score and the APACHEIII score. Arch Surg 2002;137:730736.

15. Connor S, Ghaneh P, Raraty M, et al. Increasing age andAPACHE II scores are the main determinants of outcomefrom pancreatic necrosectomy. Br J Surg 2003;90:15421548.

16. Williams M, Simms HH. Prognostic usefulness of scoringsystems in critically ill patients with severe acute pancreatitis.Crit Care Med 1999;27:901907.

17. Triester SL, Kowdley KV. Prognostic factors in acute pancre-atitis. J Clin Gastroenterol 2002;34:167176.

18. Brown A, Orav J, Banks PA. Hemoconcentration is an earlymarker for organ failure and necrotizing pancreatitis. Pancreas2000;20:367372.

19. Lankisch PG, Mahlke R, Blum T, et al. Hemoconcentra-tion: an earlymarker of severe and/or necrotizing pancreatitis?A critical appraisal. Am J Gastroenterol 2001;96:20812085.


12/13


20. de Beaux AC, Goldie AS, Ross JA, Carter DC, Fearon KC.Serum concentrations of inflammatory mediators related toorgan failure in patients with acute pancreatitis. Br J Surg1996;83:349353.

21. Pezzilli R, Billi P, Miniero R, et al. Serum interleukin-6,interleukin-8, and beta 2-microglobulin in early assessmentof severity of acute pancreatitis. Comparison with serum C-

reactive protein. Dig Dis Sci 1995;40:23412348.22. Kylanpaa-Back ML, Takala A, Kemppainen EA, et al. Procal-citonin, soluble interleukin-receptor, and soluble E-selectinin predicting the severity of acute pancreatitis. Crit Care Med2001;29:6369.

23. Tenner S, Fernandez-del Castillo C, Warshaw A, et al.Urinary trypsinogen activation peptide (TAP) predicts sever-ity in patients with acute pancreatitis. Int J Pancreatol 1997;21:105110.

24. NeoptolemosJP, Kemppainen EA,MayerJM, etal. Early pre-diction of severity in acute pancreatitis by urinary trypsinogenactivation peptide: A multicentre study. Lancet 2000;355:19551960.

25. Kemppainen E, Mayer J, Puolakkainen P, Raraty M, Slavin J,Neoptolemos JP. Plasma trypsinogen activation peptide in pa-

tients with acute pancreatitis. Br J Surg 2001;88:679680.26. Balthazar EJ. Staging of acute pancreatitis. Radiol Clin NorthAm 2002;40:11991209.

27. Balthazar EJ, Ranson JH, Naidich DP, Megibow AJ, Cacca-vale R, Cooper MM. Acute pancreatitis: Prognostic value ofCT. Radiology 1985;156:767772.

28. Balthazar EJ, Robinson DL, Megibow AJ, Ranson JH. Acutepancreatitis: Valueof CT in establishing prognosis. Radiology1990;174:331336.

29. Bradley EL 3rd. A clinically based classification system foracute pancreatitis. Summary of the International Symposiumon Acute Pancreatitis, Atlanta, Ga, September 11 through 13,1992. Arch Surg 1993;128:586590.

30. Arvanitakis M, Delhaye M, De Maertelaere V, et al. Com-puted tomography and magnetic resonance imaging in the

assessment of acute pancreatitis. Gastroenterology 2004;126:715713.31. Schmidt J, Hotz HG, Foitzik T, et al. Intravenous contrast

medium aggravates the impairment of pancreatic microcircu-lation in necrotizing pancreatitis in the rat. Ann Surg 1995;221:257264.

32. Banks PA, Gerzof SG, Langevin RE, Silverman SG, Sica GT,Hughes MD. CT-guided aspiration of suspected pancreaticinfection: Bacteriology and clinical outcome. Int J Pancreatol1995;18:265270.

33. Ashley SW, Perez A, Pierce EA, et al. Necrotizing pancreati-tis: Contemporary analysis of 99 consecutive cases. Ann Surg2001;234:572579; discussion 579580.

34. Toouli J, Brooke-Smith M, Bassi C, et al. Guidelines for themanagement of acute pancreatitis. J Gastroenterol Hepatol2001;17(Suppl):S15S39.

35. Uhl W, Warshaw A, Imrie C, et al. IAP guidelines for thesurgical management of acute pancreatitis. Pancreatology2002;2:565573.

36. TennerS, BanksPA. Acute pancreatitis: Nonsurgical manage-ment. World J Surg 1997;21:143148.

37. Brown A, Baillargeon JD, Hughes MD, Banks PA. Can fluidresuscitation prevent pancreatic necrosis in severe acute pan-creatitis? Pancreatology 2002;2:104107.

38. Goodgame JT, Fischer JE. Parenteral nutrition in the treat-ment of acute pancreatitis: Effect on complications and mor-tality. Ann Surg 1977;186:651658.

39. Lobo DN, Memon MA, Allison SP, Rowlands BJ. Evolutionof nutritional support in acute pancreatitis. Br J Surg 2000;87:695707.

40. Buchman AL, Moukarzel AA, Bhuta S, et al. Parenteral nutri-tion is associated with intestinal morphologic and functionalchanges in humans. J Parenter Enteral Nutr1995;19:453460.

41. Kalfarentzos F, Kehagias J, Mead N, Kokkinis K, Gogos CA.Enteral nutrition is superior to parenteral nutrition in severeacute pancreatitis: Results of a randomized prospective trial.Br J Surg 1997;84:16651669.

42. McClave SA, Greene LM, Snider HL, et al. Comparison ofthe safety of early enteral vs parenteral nutrition in mild acutepancreatitis. J Parenter Enteral Nutr 1997;21:1420.

43. Windsor AC, Kanwar S, Li AG, et al. Compared with paren-teral nutrition, enteral feeding attenuates the acute phaseresponse and improves disease severity in acute pancreatitis.Gut 1998;42:431435.

44. Zhao G, Wang CY, Wang F, Xiong JX. Clinical study onnutrition support in patients with severe acute pancreatitis.World J Gastroenterol 2003;9:21052108.

45. Olah A, Belagyi T, Issekutz A, Gamal ME, Bengmark S.Randomized clinical trial of specific lactobacillus and fibresupplement to early enteral nutrition in patients with acutepancreatitis. Br J Surg 2002;89:11031107.

46. EatockFC,BrombacherGD, StevenA, ImrieCW, McKayCJ,

Carter R. Nasogastric feeding in severe acute pancreatitis maybe practical and safe. Int J Pancreatol 2000;28:2329.47. Al-Omran M, Groof A, Wilke D. Enteral versus parenteral

nutrition for acute pancreatitis. Cochrane Database SystRev 2003:CD002837.

48. Mitchell RM, Byrne MF, Baillie J. Pancreatitis. Lancet 2003;361:14471455.

49. Neoptolemos JP, Carr-Locke DL, London NJ, Bailey IA,James D, Fossard DP. Controlled trial of urgent endoscopicretrograde cholangiopancreatography and endoscopic sphinc-terotomy versus conservative treatment for acute pancreatitisdue to gallstones. Lancet 1988;2:979983.

50. Fan ST, Lai EC, Mok FP, Lo CM, Zheng SS, Wong J.Early treatment of acute biliary pancreatitis by endoscopicpapillotomy. N Engl J Med 1993;328:228232.

51. Folsch UR, Nitsche R, Ludtke R,Hilgers RA, Creutzfeldt W.Early ERCP and papillotomy compared with conservativetreatment for acute biliary pancreatitis. The German StudyGroup on Acute Biliary Pancreatitis. N Engl J Med 1997;336:237242.

52. Mergener K, Baillie J. Endoscopic treatment for acute biliarypancreatitis. When and in whom? Gastroenterol Clin NorthAm 1999;28:601613.

53. Varghese JC, Farrell MA, Courtney G, Osborne H,Murray FE, Lee MJ. Role of MR cholangiopancreatographyin patients with failed or inadequate ERCP. Am J Roentgenol1999;173:15271533.

54. Bradley EL 3rd, Allen K. A prospective longitudinal study ofobservation versus surgical intervention in the managementof necrotizing pancreatitis. Am J Surg1999;161:1914; discus-sion 2425.

55. Lumsden A, Bradley EL 3rd. Secondary pancreatic infec-tions. Surg Gynecol Obstet 1990;170:459467.

56. Bassi C, Falconi M, Talamini G, et al. Controlled clinical trialof perfloxacin versus imipenem in severe acute pancreatitis.Gastroenterology 1998;115:15131517.

57. Grewe M, Tsiotos GG, Luque de-Leon E, Sarr MG. Fungalinfection in acute necrotizing pancreatitis. J Am Coll Surg1999;188:408414.

58. Ratschko M, Fenner T, Lankisch PG. The role of antibioticprophylaxis in the treatment of acute pancreatitis. Gastroent-erol Clin North Am 1999;28:641659.

59. Bassi C, LarvinM, VillatoroE. Antibiotic therapy for prophy-laxis against infectionof pancreatic necrosis in acute pancreati-tis. Cochrane Database Syst Rev 2003:CD002941.


13/13


60. Buchler M, Malfertheiner P, Friess H, et al. Human pancre-atic tissue concentration of bactericidal antibiotics. Gastroen-terology 1992;103:19021908.

61. Pederzoli P, Bassi C, Vesentini S, Campedelli A. A random-izedmulticenter clinical trial of antibioticprophylaxis of septiccomplications in acute necrotizing pancreatitis with imi-penem. Surg Gynecol Obstet 1993;176:480483.

62. Saino V, Kemppainen E, Puolakkainen P, et al. Early antibi-otic treatment in acute necrotizing pancreatitis. Lancet 1995;346:663667.

63. Schwarz M, Isenmann R, Meyer H, Beger HG. Antibioticuse in necrotizing pancreatitis. Results of a controlled study.Dtsch Med Wochenschr 1997;122:356361.

64. Isenmann R, Runzi M, Kron M, et al. Prophylactic antibiotictreatment in patients with predicted severe acute pancreatitis:A placebo-controlled, double-blind trial. Gastroenterology2004;126:9971004.

65. Golub R, Siddiqi F, Pohl D. Role of antibiotics in acutepancreatitis: A meta-analysis. J GASTRO INTEST SURG 1998;2:496503.

66. Sharma VK, Howden CW. Prophylactic antibiotic adminis-tration reduces sepsis and mortality in acute necrotizing pan-creatitis: A meta-analysis. Pancreas 2001;22:2831.

67. Powell JJ, Campbell E, Johnson CD, Siriwardena AK. Surveyof antibiotic prophylaxis in acute pancreatitis in the UK andIreland. Br J Surg 1999;86:320323.

68. Gloor B, Muller CA, Worni M, et al. Pancreatic infection insevere pancreatitis: The role of fungus and multiresistantorganisms. Arch Surg 2001;136:592596.

69. Rau B, Uhl W, Buchler MW, Beger HG. Surgical treatmentof infected necrosis. World J Surg 1997;21:155161.

70. He YM, Lv XS, Ai ZL, et al. Prevention and therapy offungal infection in severe acute pancreatitis: A prospectiveclinical study. World J Gastroenterol 2003;9:26192621.

71. Lange JF, van Gool J, Tytgat GN. The protective effect ofa reduction in intestinal flora on mortality of acute haemo-rrhagic pancreatitis in the rat. Hepatogastroenterology 1987;34:2830.

72. Luiten EJ, Hop WC, Lange JF, Bruining HA. Controlledclinical trial of selective decontamination for the treatmentof severe acute pancreatitis. Ann Surg 1995;222:5765.

73. Fernandez-del Castillo C, Rattner DW, Makary MA, Mosta-favi A, McGrath D, Warshaw AL. Debridement and closedpacking for the treatment of necrotizing pancreatitis. AnnSurg 1998;228:676684.

74. Branum G, Galloway J, Hirchowitz W, Fendley M, Hunter J.Pancreatic necrosis: Results of necrosectomy, packing, andultimate closure over drains. Ann Surg 1998;227:870877.

75. Rattner DW, Legermate DA, Lee MJ, Mueller PR, Wars-haw AL. Early surgical debridement of symptomatic pancre-atic necrosis is beneficial irrespective of infection. Am J Surg1992;163:105109; discussion 109110.

76. McFadden DW, Reber HA. Indications for surgery in severe

acute pancreatitis. Int J Pancreatol 1994;15:8390.77. Rau B, Pralle U, Uhl W, Schoenberg MH, Beger HG. Man-agement of sterile necrosis in instances of severeacute pancre-atitis. J Am Coll Surg 1995;181:279288.

78. Ashley SW. Sterile pancreatic necrosis: Is operation neces-sary? J Am Coll Surg 1995;181:363364.

79. Warshaw AL. Pancreatic necrosis: To debride or not to de-bridethat is the question. Ann Surg 2000;232:627629.

80. Isenmann R, Rau B, Zoellner U, Beger HG. Managementof patients with extended pancreatic necrosis. Pancreatology2001;1:6368.

81. Mier J, Leon EL, Castillo A, Robledo F, Blanco R. Earlyversus late necrosectomy in severe necrotizing pancreatitis.Am J Surg 1997;173:7175.

82. Baron TH, Morgan DE, Vickers SM, Lazenby AJ. Organizedpancreatic necrosis: Endoscopic, radiologic, and pathologicfeatures of a distinct clinical entity. Pancreas 1999;19:105108.

83. Sarr MG, Nagorney DM, Mucha P Jr, Farnell MB, JohnsonCD. Acute necrotizing pancreatitis: Management by planned,staged pancreatic necrosectomy/debridement and delayedprimary wound closure over drains. Br J Surg 1991;78:576581.

84. Beger HG. Operative management of necrotizing pancreati-tisnecrosectomy and continuous closed postoperativelavageof the lesser sac. Hepatogastroenterology 1991;38:129133.

85. Beger HG, Isenmann R. Surgical management of necrotizingpancreatitis. Surg Clin North Am 1999;79:800, ix.

86. Freeny PC, Hauptmann E, Althaus SJ, Traverso LW, Sina-nan M. Percutaneous CT-guidedcatheter drainage of infectedacute necrotizing pancreatitis: Techniques and results. Am JRoentgenol 1998;170:969975.

87. Baron TH,Harewood GC,Morgan DE, Yates MR.Outcomedifferences after endoscopic drainage of pancreatic necrosis,acute pancreatic pseudocysts, and chronic pancreatic pseu-docysts. Gastrointest Endosc 2002;56:717.

88. Seifert H, Wehrmann T, Schmitt T, Zeuzem S, Caspary WF.Retroperitoneal endoscopic debridement for infected peri-pancreatic necrosis. Lancet 2000;356:653655.

89. Kozarek RA. Endotherapy for organized pancreatic necrosis:

Perspective on skunk-poking. Gastroenterology 1996;111:820823.

90. Gambiez LP, Denimal FA, Porte HL, Saudemont A, Cham-bon JP, Quandalle PA. Retroperitoneal approach and endo-scopic management of peripancreatic necrosis collections.Arch Surg 1998;133:6672.

91. Zhou ZG,Zheng YC,Shu Y, et al.Laparoscopic managementof severe acute pancreatitis. Pancreas 2003;27:e46e50.

92. Sax HC, Warner BW, Talamini MA, et al. Early total paren-teral nutrition in acute pancreatitis: Lack of beneficial effects.Am J Surg 1987;153:117114.

93. de Beaux AC, ORiordain MG, Ross JA, Jodozi L, Carter DC,Fearon KC. Glutamine-supplemented total parenteral nutri-tion reduces blood mononuclear cell interleukin-8 release in

severe acute pancreatitis. Nutrition 1998;14:261265.94. Delcenserie R, Yzet T, Ducroix JP. Prophylactic antibioticsin treatment of severe acute alcoholic pancreatitis. Pancreas1996;13:198201.

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