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402
which evaluate early versus delayed cholecystectomy in patients with mild pancreatitis (Table 36.2 ).
Tang and colleagues were among the fi rst to publish their experiences in 1995,
retrospectively examining outcomes and incidence of surgical morbidity in patients
operated on within 1 week of symptom onset [ 11 ]. Patients were categorized accord-
ing to severity of pancreatitis using Ranson’s criteria [ 12 ], and underwent either
early (<1 week since symptom onset) or delayed (>1 week since symptom onset)
laparoscopic cholecystectomy . All operations were performed during the index
admission, at least 48 h after biochemical and clinical resolution of pancreatitis.
Among patients categorized as “mild” pancreatitics (<3 Ranson criteria), there was
no signifi cant difference in surgical morbidity, conversion to open operation, mortality , or post operative length of stay between groups undergoing early and delayed
laparoscopic cholecystectomy. Patients who underwent early cholecystectomy were
noted to have a signifi cantly shorter overall hospitalization. Since Teng’s seminal
paper, numerous retrospective reviews have arrived at similar results, advocating
same-admission laparoscopic cholecystectomy for stable patients with resolved
mild, or interstitial/edematous pancreatitis.
Some have advocated for earlier laparoscopic cholecystectomy in carefully
selected patients. Taylor and colleagues reported on a group of retrospectively
examined patients who presented with mild gallstone pancreatitis and were operated on either after complete normalization of the physical exam and serum amylase, or after physical examination and serum amylase had begun to trend towards
normalization [ 13 ]. Patients in the early cholecystectomy group were operated on
an average of 1.8 days after presentation and were found to have a signifi cantly
shorter overall hospitalization than those who were postponed for complete resolution of pancreatitis. Additionally, no benefi t was found when postponing intervention until complete resolution of pancreatitis.
To date, one randomized controlled trial has addressing the timing of laparoscopic cholecystectomy in patients with acute biliary pancreatitis . In 2012, Aboulian
and colleagues reported on 50 patients that presented with mild gallstone pancreatitis , defi ned by fewer than three Ranson criteria, who were randomized to either
early laparoscopic cholecystectomy within the fi rst 48 h of admission, or to cholecystectomy after symptom and laboratory resolution of pancreatitis [ 14 ]. Patients
received intervention as long as post admission serum amylase values documented
stable pancreatitis. The early surgery group was operated on at a mean of 35 h compared to 77.8 h in the control group. Overall hospital stay was signifi cantly shorter
in the early operative group (3.8 vs. 5.8 days, P = 0.0016). No patients were readmitted, had post-operative complications, or required conversion to open operation. At
interim analysis (50 of 100 total patients), the study was terminated due to the signifi cant decrease in total hospitalization without increased morbidity among the
early operation group. As with previous retrospective, non-randomized studies,
results indicate that cholecystectomy can be safely performed in patients with mild
pancreatitis soon after admission, and that delaying operation until full symptomatic and biochemical resolution is unnecessary and adds to hospital stay.
D.S. Bryan and M. Hussain
403
Table 36.2 Clinical outcomes in patients with interstitial edematous/mild ABP with early versus delayed cholecystectomy
Author (year) N
Time until
operation (d)
Success
( laparoscopic
completion) LOS (d) Morbidity Mortality
Pancreatitis
severity grading
Study type ( quality of
evidence)
Tang (1995)
[
11 ]
122 <7 (early) 114/122 (93 %) 7.8 (early) 0 0 Ranson <3 Retrospective cohort
(low)
>7 (late) 14 (late)
Uhl (1999) [
18 ] 35 10 30/35 (86 %) 5 1/30 (3 %) 0 CT Prospective
observational (low)
Taylor (2004)
[
13 ]
46 1.8 (early) 26/26 (100 %) 3.5 (early) 3/26 (11 %) 0 Ranson <3 Retrospective
observational (low)
2.3 (late) 18/20 (90 %) 4.7 (late) 2/20 (10 %)
Griniatsos
(2005) [
27 ]
44 7–14 (early) 20/20 (100 %) 2 (post-op) 1/20 (5 %) 0 Glasgow <3 Retrospective cohort
(low)
60 (late) 24/24 (100 %) 2 (post-op) 1/24 (4 %)
Rosing (2007)
[
28 ]
220 <2 (early) 40/41 (98 %) 4 1/20 (5 %) 0 Ranson <3 Prospective cohort
(medium)
5 (late) 177/177 (100 %) 7 (post-op) 1/41 (2.4 %)
Aboulian
(2010) [
14 ]
49 1.8 (early) 25/25 (100 %) 3.5 0/25 0 Ranson <3 Randomized
controlled trial (high)
3.2 (late) 24/24 (100 %) 5.8 0/24
Falor (2012)
[
29 ]
303 <2 (early) 114/117 (97 %) 3 5/117 (4.2 %) 0 Ranson <3 Retrospective cohort
(low)
>2 (late) 172/186 (93 %) 6 9/186 (4.8 %)
Mador (2014)
[
25 ]
80 3.3 43/45 (96 %) 8.8 4/45 (9 %) 0 Ranson <3 Retrospective
observational (low)
141 32/35 (91 %) 10 5/35 (15 %)
36 Early or Delayed Cholecystectomy in Acute Gallstone Pancreatitis
404
Patients with Severe or Necrotizing Pancreatitis
As with patients with more mild disease, those with severe or necrotizing gallstone
pancreatitis should undergo clearance of the common duct and cholecystectomy
after disease stabilization [ 15 ]. With 10–20 % of patients with gallstone pancreatitis
developing necrotizing pancreatitis and systemic organ failure, timing of surgical
intervention differs from those with less severe disease [ 16 , 17 ]. Few studies exist
evaluating the timing of laparoscopic cholecystectomy in patients with severe or
necrotizing pancreatitis. Three were identifi ed and included for review (Table 36.3 ).
In the classic paper by Kelly and Wagner published in 1988, patients with acute
gallstone pancreatitis were randomized to early (<48 h) or delayed (>48 h) open
cholecystectomy [ 5 ]. Those with severe acute pancreatitis (greater than 3 Ranson
criteria) randomized to the early surgery group were found to have signifi cantly
higher rates of morbidity and mortality . Numerous other retrospective studies were
published in the 1970s and 1980s detailing the dangers associated with open cholecystectomy in those with acute, active, severe pancreatitis.
These fi ndings were translated to the laparoscopic era with Tang’s paper in 1995
[ 11 ]. A subset of patients with severe gallstone pancreatitis (>3 Ranson’s criteria)
underwent early (<1 week) or delayed laparoscopic cholecystectomy . Those in the
early surgery group had a signifi cantly increased overall length of hospital stay.
In 1999 Uhl and colleagues published a retrospective report on 60 patients with
acute biliary pancreatitis [ 18 ]. All received cross sectional imaging (contrast
enhanced CT scanning) and were categorized as having necrotizing pancreatitis or
acute interstitial pancreatitis. Of the 21 with necrotizing disease, 13 underwent laparoscopic cholecystectomy an average of 14 days after symptom onset. Five of thirteen (38 %) required conversion to an open operation. The remainder underwent
open cholecystectomy at the time of necrosectomy. Extent of necrosis demonstrated
on CT was shown to correlate with the development of infected pancreatic necrosis .
The authors recommend postponing laparoscopic cholecystectomy for at least
7 days in the case of necrotizing pancreatitis, and for at least 3 weeks in patients
with extended pancreatic necrosis involving more than 50 % of the gland due to an
increased risk for late development of pancreatic necrosis.
The Role for Endoscopic Sphincterotomy
It remains clear that both open and laparoscopic intervention in patients with severe
and necrotizing pancreatitis is morbid. Delaying cholecystectomy after discharge in
patients with resolved pancreatitis is similarly risky and has been recognized to be
associated with a signifi cant risk of recurrent biliary events, occurring in 30–50 %
of patients within the fi rst 2 months [ 16 , 19 ]. As recurrent acute pancreatitis in
patients with prior severe or necrotizing disease can prove fatal, endoscopic sphincterotomy performed during initial admission has been proposed as a bridging procedure to interval cholecystectomy.
D.S. Bryan and M. Hussain
405
Table 36.3 Clinical outcomes in patients with necrotizing/moderately severe to severe ABP with early versus delayed cholecystectomy
Author (year) N
Time until
operation
(days) Success LOS (days) Morbidity Mortality
Pancreatitis
severity grading Study type ( quality of evidence)
Tang (1995) [
11 ] 9 (early) 4.2 (early) 3/9 (33 %) 9.8 1/9 (11 %) 0/9 Ranson >3 Retrospective cohort (low)
11 (late) 9.8 (late) 9/11 (82 %) 11.9 0/11 (0 %) 0/11
Uhl (1999) [
18 ] 13 14 8/13 (62 %) 6 2/8 (25 %) 0/8 CT Prospective observational (low)
Heider (2005) [
16 ] 30 102 25/27 (93 %) 3 2/27 (3 %) 0 CT Retrospective observational (low)
36 Early or Delayed Cholecystectomy in Acute Gallstone Pancreatitis
406
Several studies have addressed the utility of ES in patients with acute gallstone
pancreatitis . Those who undergo ES prior to discharge are less likely to have recurrent episodes of pancreatitis, however are not spared from all biliary complications
secondary to gallstones [ 6 , 20 ]. In looking at patients with interstitial edematous
pancreatitis with fl uid collections, as well as patients with necrotizing pancreatitis,
Heider and colleagues found that 23 % of those who had received endoscopic
sphincterotomy were readmitted after discharge, but prior to eventual cholecystectomy [ 16 ]. While multiple patients experienced biliary symptomatology ( cholangitis , pain , nausea/emesis, and infected peri-pancreatic fl uid collections), there were
no noted episodes of recurrent pancreatitis.
Some have advocated endoscopic retrograde cholangiopancreatography and
endoscopic sphincterotomy for all patients with acute gallstone pancreatitis . A
Cochrane review in 2012 examined the role for early ERCP , defi ned as conservative
medical management with the addition of ERCP within the fi rst 72 h of admission
[ 21 ]. A total of 7 trials and 757 patients were included in the review. The early
ERCP strategy, when applied broadly to all presenting patients, was not found to
reduce morbidity or mortality when compared to normal conservative management.
The potential benefi t of decreased local complications (i.e. fl uid collections) and
systemic complications was identifi ed when the strategy was applied to subgroups
of patients with suspected cholangitis or suspected persistent choledocholithiasis .
Cost Implications
The incidence of both gallstone disease and pancreatitis in the United States and the
western world are increasing, which has been hypothesized to be secondary to
increasing trends in obesity [ 2 , 22 , 23 ]. An estimated 700,000 cholecystectomies are
performed annually at a cost of $6.5 billion [ 24 ]. With changing healthcare land-
scapes and payor structures, it is important to acknowledge the impact of management decisions on total cost of care.
A signifi cant cost is associated with recurrent biliary symptomatology. The risk
of recurrent symptoms and readmissions is not negligible, and must be considered
in patients with resolved pancreatitis awaiting interval cholecystectomy . Recurrent
pancreatitis has been reported to occur with a frequency of roughly 10 %, and overall biliary complication rates have been reported to be as high as 60 % in patients
waiting 20 weeks for cholecystectomy [ 8 , 25 ].
The patients most likely to experience cost savings secondary to early cholecystectomy are those with mild biliary pancreatitis [ 16 ]. A recently published UK study
considered treatment costs associated with laparoscopic cholecystectomy performed at various intervals. Total cost of care for patients undergoing defi nitive
operation within the fi rst 3 days of symptom onset was compared with cost of care
for patients undergoing subsequent admission (interval) cholecystectomy. Early
intervention was found to yield a cost savings of nearly 27 % [ 26 ].
D.S. Bryan and M. Hussain
407
Recommendations
Management of patients with acute gallstone pancreatitis can be stratifi ed according
to severity. Those with mild biliary pancreatitis , without systemic complications or
organ failure, are appropriate for evaluation for early laparoscopic cholecystectomy .
To date, multiple retrospective and observational studies have compared early and
delayed surgery in patients with mild gallstone pancreatitis, however there is a paucity of prospective evidence, with a single randomized trial in the literature. Based
on the available data, we make a recommendation for laparoscopic cholecystectomy
within the fi rst 2 days of admission, provided the patient has shown clinical stability.
Among patients with mild disease, further delay appears to add to total cost of care
and length of stay.
In patients with severe, or necrotizing pancreatitis, there is inadequate evidence
to recommend an appropriate interval for laparoscopic cholecystectomy following
resolution of the acute disease.
A Personal View of the Data
Therapy for gallstone pancreatitis includes patient resuscitation, clearance of the
common bile duct (if necessary), and cholecystectomy to remove the nidus for
future attacks. Pancreatitis represents a spectrum of disease and severity varies
greatly, and multiple severity grading systems exist. Ranson’s criteria, though outdated, are the most frequently used in the literature to risk stratify patients with
gallstone pancreatitis. Among those with mild disease (commonly defi ned as <3
Ranson’s criteria), which has been shown to be stable by physical examination and
laboratory values, laparoscopic cholecystectomy should be pursued, regardless of
the time since symptom onset. Patients with suspected choledocholithiasis should
undergo ERCP and ES. Those with severe or necrotizing pancreatitis should be
initially resuscitated and stabilized. When performed after stabilization and prior to
hospital discharge, ERCP and ES can provide an important bridge to eventual laparoscopic cholecystectomy.
Recommendations
• Patients with mild gallstone pancreatitis that is stable in severity should undergo
laparoscopic cholecystectomy at earliest convenience, provided they are of
acceptable surgical risk (evidence quality moderate; strong recommendation).
• Patients with severe or necrotizing gallstone pancreatitis should undergo interval
cholecystectomy with endoscopic ERCP and ES utilized as a bridging proce-
dure, if necessary (evidence quality low; weak recommendation).
36 Early or Delayed Cholecystectomy in Acute Gallstone Pancreatitis
408
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surgery. Surgery. 1988;104:600–4.
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36 Early or Delayed Cholecystectomy in Acute Gallstone Pancreatitis
411© Springer International Publishing Switzerland 2016
J.M. Millis, J.B. Matthews (eds.), Diffi cult Decisions in Hepatobiliary
and Pancreatic Surgery, Diffi cult Decisions in Surgery: An Evidence-Based
Approach, DOI 10.1007/978-3-319-27365-5_37
Chapter 37
Nutritional Support in Acute Necrotizing
Pancreatitis
Andreas Mykoniatis
Abstract Enteral nutrition (EN) is now considered the standard of care for patients
with severe acute pancreatitis and patients with pancreatic necrosis. Several randomized controlled trials and meta-analyses have shown that the administration of
EN nutrition reduces complications and mortality of patients with severe pancreatitis including patients with pancreatic necrosis compared to parenteral nutrition
(PN). PN had been the standard of care for many decades, based on the concept of
“pancreatic rest”. Avoidance of alimentary stimulation of pancreatic exocrine secretion was assumed to limit or prevent ongoing pancreatic infl ammation. Current
practice guidelines recommend the use of enteral nutrition for feeding patients with
acute pancreatitis, including those with pancreatic necrosis. Accumulating evidence
suggests that the use of the gut through EN may promote the maintenance of gut
barrier and immune functions. Provision of luminal nutrition via the gastric approach
appears to be equally tolerated as the enteral route and may be more cost effective.
However, larger randomized controlled trials and other studies focused on optimization of nutritional support during the acute and convalescent phases of necrotizing
pancreatitis are needed. Pharmaconutriton or the use of defi ned elemental formulae
has not yet been shown to be benefi cial. The use of PN should be limited to patients
that cannot tolerate EN.
Keywords Acute pancreatitis • Pancreatic necrosis • Enteral nutrition • Parenteral
nutrition • Enteral feedings • Parenteral feedings • Severe pancreatitis
A. Mykoniatis (*)
Department of Medicine , The University of Chicago Medicine ,
5841 S. Maryland Ave. Rm. M408, MC4076 , Chicago , IL 60637 , USA
e-mail:
amykonia@medicine.bsd.uchicago.edu
412
Introduction
Patients with severe acute pancreatitis are defi ned as those with ≥3 Ranson criteria;
APACHE II score of ≥8; and a CRP level of ≥150 mg/dl [ 1 ]. The Atlanta classifi ca-
tion [ 2 ] determines the severity of acute pancreatitis by the presence of organ fail-
ure, systemic failure, or other prognostic indicators (i.e.:≥3 Ranson criteria or
APACHE II ≥8). The revised Atlanta classifi cation includes the use of morphologic
CECT (Contrast-enhanced computed tomography ) criteria to diagnose acute necrotizing pancreatitis by the presence of necrosis and evidence of infection.
The exact pathophysiology [ 3 ] of acute pancreatitis (AP) is not clear, but it is
thought to be caused by the abnormal activation of pancreatic proenzymes that
results in autodiegestion of the pancreas. In theory, “pancreatic rest” might help
decrease pancreatic exocrine secretion and thereby retard disease progression. It is
now known that several other factors are involved in the progression of pancreatitis
that involve the integrity of the intestinal mucosa [ 4 ].
In about 15–20 % of patients, the disease progresses to severe illness with a prolonged disease course; multiple organ failure; and sepsis. The overall mortality of
AP is about 5 % and can reach up to 20–30 % in patients with severe AP and infected
necrosis [ 5 , 6 ]. Parenteral nutrition was regarded as the standard nutritional man-
agement for many decades based on the theory of pancreatic rest [ 7 ]. Optimal man-
agement now includes resuscitation with IV fl uids, pain management, and early
enteral nutrition . Several pieces of evidence have shown that early enteral nutrition
is superior to PN. Enteral nutrition (EN) preserves mucosal integrity and reduces
the risk of infections. In comparison to PN, EN seems to be equally tolerated and is
more cost effective. This chapter will address and grade the evidence for the use of
enteral nutrition in patients with severe acute pancreatitis and pancreatic necrosis . It
will also evaluate the existing evidence for the use of gastric vs. jejunal tube feeding
(TF); early vs. late nutrition; and the use of polymeric vs. elemental formula and
probiotics in the setting of severe acute pancreatitis and pancreatic necrosis.
Search Strategy
In order to evaluate the use of enteral nutrition , a literature search of English language publications from 2000 to 2013 was used to identify published data on acute
pancreatitis and nutrition using the PICO outline (Tables
37.1 and 37.2 ). Databases
searched were PubMed, Web of Sciences, Cochrane library, and Embase Database.
Terms used in the search were “acute pancreatitis,” “ pancreatic necrosis ”, “enteral
nutrition/ parenteral nutrition ”, or “enteral feeding/ parenteral feedings ”. Eight randomized controlled trials were included in the analyses that evaluated the use of EN
vs. PN. Four randomized controlled trials that studied the use of NG vs. NJ tube
feeds in patients with acute pancreatitis were included. The data was classifi ed
using the GRADE system.
A. Mykoniatis