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Table 37.1 PICO table for enteral nutrition vs. parenteral nutrition in acute pancreatitis
P (Patients) I (Intervention)
C (Comparator
group) O (Outcomes measured)
Patients with severe
acute pancreatitis
Enteral Parenteral nutrition Mortality, organ failure,
pancreatic infection
Table 37.2 PICO table for G tube vs. J tube in acute pancreatitis
P (Patients) I (Intervention) C (Comparator group) O (Outcomes measured)
Patients with acute
pancreatitis
Gastric Jejunal Incidence of infection
Results
Feeding in Severe Acute Pancreatitis and Pancreatic Necrosis-EN vs. PN
The data supporting the use of EN are based on more than eight prospective randomized controlled trials. In particular, comparison of PN to EN in patients with
severe acute pancreatitis has been addressed by these trials [ 8 – 15 ] (Table 37.3 ); and
the results were analyzed in several meta-analyses [ 16 – 18 ].
In the most recent randomized study by Wu et al. [ 14 ], 107 patients were enrolled
between 2003 and 2007. Fifty-four patients were fed with PN and 53 patients were
fed with EN. Those individuals with pancreatic necrosis determined by CT scan and
confi rmed by a C-reactive protein (CRP) level (greater than 19.5 mg/dL, 48 h after
the onset of the disease), were included in this study. Eighty percent of the patients
developed organ failure in the PN group vs. 21 % (P < 0.05) in the EN group.
Similarly, 80 % and 22 % (P < 0.05) in the PN and EN groups respectively underwent surgical intervention. Seventy-two percent of the PN patients (P < 0.05) and
23 % of the EN patients developed pancreatic septic necrosis. The mortality rate in
the PN and EN groups was 43 % and 11 % respectively.
In a meta-analysis by Petrov et al. [ 18 ] published in 2008, the aim was to evalu-
ate PN and EN with regards to infectious complication and mortality . Five randomized controlled trials compared parenteral to enteral nutrition in patients with
predicted severe acute pancreatitis . EN reduced the risk of infectious complications
(relative risk, 0.47; 95 % CI, 0.28–0.77; P < 0.001); pancreatic infections (0.48;
0.26–0.91; P = 0.02); and mortality (0.32; 0.11–0.98; P = 0.03).
According to the international consensus guideline committee [ 19 ] that pub-
lished their guidelines in 2012, there was almost uniform agreement on the following items. Patients with mild to moderate disease should be treated with IV fl uids
and nil per os (NPO) with gradual advancement of their diet. The need for EN or PN
therapy should be considered in mild to moderate disease when the patient has been
NPO for 5–7 days. In severe disease, EN should be started early with a small
37 Nutritional Support in Acute Necrotizing Pancreatitis
414
peptide- based medium-chain triglyceride (MCT) oil formula into the stomach or
small intestine. EN can be continued despite the presence of complications such as
fi stula, ascites , or pseudocyst. PN should be initiated if EN is contraindicated or not
well tolerated. The guidelines conclude that EN is the evidence based standard of
care for patients with severe acute pancreatitis and pancreatic necrosis .
Route of Enteral Feeding in Acute Pancreatitis-NG vs. NJ
The administration of nasogastric (NG) tube feeding does not require specialized
invasive procedures. However, it is thought to increase the risk of aspiration resulting in prolonged hospitalization. Conversely, the provision of nasojejunal (NJ) tube
feeds usually requires the insertion of a NJ tube that requires endoscopic or radiological guidance for insertion, procedures that may delay the initiation of feeding.
The effect of NG vs. NJ tube feeds has been investigated in four randomized
clinical studies (Table 37.4 ) [ 20 – 23 ]. These studies included patients with severe
acute pancreatitis (SAP) and pancreatic necrosis . There were no signifi cant differences in clinical outcomes or in tolerance.
In the most recent randomized controlled study published by Singh et al. in 2012
[ 22 ], 78 patients were randomized to feeding by either the NG or the NJ route. This
was a non-inferiority study. Thirty-six of the patients had necrotizing pancreatitis.
Early enteral feeding through NG was not inferior to NJ in patients with SAP. The
presence of infectious complications in the NG and NJ groups was 23.1 % and
35.9 % (P < 0.05) respectively. The infectious complications were within the
Table 37.3 Clinical outcomes of EN vs. PN
Author (year)
EN PN
Results
Study type ( quality
of evidence) N a N a
Kalfarent-zos et al.
(1997)
18 20 Lower pancreatic infection and sepsis
rate in EN
Prospective (high)
Gupta (2003) 8 9 Non-signifi cant lower pancreatic
infection rate in EN
Prospective (high)
Louie (2005) 10 18 Non-signifi cant lower pancreatic
infection rate in EN
Prospective (high)
Eckerwall (2006) 23 25 Signifi cant higher pancreatic infection
rate in EN
Prospective (high)
Petrov (2007) 35 34 Signifi cant lower pancreatic infection
and mortality rate in EN
Prospective (high)
Casas (2007) 11 11 Non-signifi cant lower pancreatic
infection rate and length of stay
Prospective (high)
Doley (2008) 25 25 Non-signifi cant pancreatic infection
and mortality rate
Prospective (high)
Wu (2010) 53 54 Signifi cant lower pancreatic necrosis
rate in EN
Prospective (high)
a
N: number of patients
A. Mykoniatis
415
non- inferiority limit. All other complications such as pain in refeeding intestinal
permeability and endotoxemia were comparable in both groups.
In the meta-analysis published by Petrov [ 24 ], four studies [ 20 – 25 ] investigated
the use of NG tube feedings, and a total of 92 patients with predicted severe acute
pancreatitis were included. Eleven of those patients (16.9 %) had severe necrotizing
pancreatitis. There was no statistically signifi cant difference in the mortality rate
(RR = 0.77; 95 % CI: 0.37–1.62; P = 0.50) between the patients fed via NG vs.
NJ. Likewise, there was no difference in the feeding tolerance in the two groups
(RR = 1.09; 95 % CI: 0.46–2.59; P = 0.84).
A meta-analysis published by Zhang et al. [ 26 ] in June 2013 included many stud-
ies in nutrition in the ICU setting and showed that jejunal feeding can deliver a
higher proportion of the estimated energy requirement compared to gastric feeding.
However, mortality (OR, 1.05; 95 % CI, 0.77–1.44); new-onset pneumonia (OR,
0.77; 95 % CI, 0.53–1.13); and aspiration (OR, 1.20; 95 % CI, 0.64–2.25) were not
improved in the NJ tube feed group.
The concept of NG vs. NJ tube feeds needs to be further investigated in a large
randomized trial that is adequately powered. As stated by Petrov et al. [ 27 ], this
will require the enrollment of 440 patients to demonstrate a 10 % absolute risk
reduction in feeding intolerance. Such a study is technically diffi cult requiring
multicenter involvement. Current randomized studies each have fl aws that were
discussed by Petrov [ 28 ]. For example, the study by Eatock [ 21 ] used a duodenal
and not jejunal tube. In the study by Kumar [ 23 ] and Singh [ 22 ], there was a delay
in initiating the TF.
The practical preference of using NJ rather than NG feeds in patients with necrotizing pancreatitis is related to the clinical observation that necrotizing pancreatitis patients commonly develop gastric ileus [ 29 ]. Therefore, they are at an increased
risk for non-tolerance to NG tube feeds. In addition, the use of NJ tube feeds is
intuitively more consistent with the concept of pancreatic rest which is an area of
ongoing investigation. However, hard data showing the advantage of NJ over NG
routes has not yet been established.
The anatomic level below which pancreatic stimulation is prevented is another
area that requires further investigation. There was a loss of pancreatic stimulatory
Table 37.4 Clinical outcomes of NG vs. NJ tube feedings
Author (year)
NG NJ
Results
Study type ( quality of
evidence) N* N*
Eatock (2000) 20 18 Non-signifi cant differences in
outcome and tolerance
Cohort (low)
Eatock (2005) 9 8 Non-signifi cant difference in
pancreatic infection rate and tolerance
Prospective (low due
to fl aws)
Kumar (2006) 15 16 Non-signifi cant difference in outcome
measure and tolerance
Prospective (low due
to fl aws)
Singh (2012) 39 39 Infectious complication within the
inferiority limit and similar tolerance
Prospective (low due
to fl aws)
* = number of patients
37 Nutritional Support in Acute Necrotizing Pancreatitis
416
effect from 20 to 120 cm post ligament of Treitz as stated by O’Keefe et al. [ 30 ]. A
study by Kumar et al. [ 23 ] that aimed to investigate the stimulatory effects of feed-
ing by inserting NJ tubes 60 cm beyond the ligament of Treitz was inconclusive due
to inadequate statistical power.
There is a weak recommendation for NJ tube feed placement in patients with
severe acute pancreatitis and pancreatic necrosis because of possible gastric ileus
resulting in inadequate nutrition. The optimal length of the feeding tube insertion
below the ligament of Treitz has to be further investigated.
Type of TF
There are multiple tube feeding products available. These can be divided into three
large groups. These groups include the elemental or semielemental; polymeric; and
immunomodulating products (i.e., glutamine, omega-3 fatty acids, antioxidants, or
probiotics) [ 31 ].
The use of an elemental or semielemental formulation during the treatment of
severe acute pancreatitis was thought to be advantageous because it was absorbed
easier resulting in better tolerance. On the other hand, polymeric formulations are
less expensive. In a meta-analyses published by Petrov et al. [ 32 ], the different feed-
ing products were compared with respect to their feeding tolerance. The following
endpoints were evaluated: temporary reduction or cessation of feeding; infectious
complications; and in-hospital mortality . The study reviewed 20 randomized controlled trials and included a total of 1070 patients with acute pancreatitis. Eighthundred twenty-fi ve of the patients had severe acute pancreatitis. In the study, it was
shown that the use of an elemental formulation did not result in a statistically signifi cant difference in the risk of infectious complications and death. Polymeric and
elemental formulations were equally tolerated.
The use of probiotics was studied in a multicenter randomized double blind controlled trial entitled PROPATRIA [ 33 ]. In this study, 298 patients with predicted
severe acute pancreatitis were randomized to receive either a multispecies probiotic
preparation or placebo for 28 days. The primary endpoints were infectious complications (infected pancreatic necrosis , bacteremia, pneumonia, urosepsis, or infected
ascites ) during admission and at 90-day follow-up. Infectious complications
occurred in 30 % of patients in the probiotics group and 28 % in the placebo group.
Sixteen percent of patients in the probiotics group died, compared with 6 % in the
placebo group. In addition, nine patients in the probiotics group developed bowel
ischemia compared with none in the placebo group. The PROPATRIA study was
preceded by two lower powered studies by Olah et al. [ 34 , 35 ] that showed decreased
rates of infected necrosis; hospital stay; SIRS; and organ failure in patients with
acute pancreatitis using lactobacillus. Because of the confl icting results of these
studies, and the surprising yet unexplained increase in death and intestinal ischemia
in the PROPATRIA study, the use probiotic prophylaxis in patients with severe
acute pancreatitis remains highly controversial and in need of further investigation.
A. Mykoniatis
417
Timing of Feeding Initiation- Early vs. Late
The role of very early (in the fi rst 24 h) EN in patients with severe acute pancreatitis
has yet to be adequately investigated in randomized trials. The initiation of TF in the
fi rst 24–48 h after admission is the current practice of timing enteral nutrition
support.
Initiation of very early enteral nutrition in patients with severe pancreatitis is
thought to prevent mucosal barrier dysfunction; bacterial overgrowth; and bacterial
translocation. This concept was examined in a meta-analysis by Bakker [ 36 ] that
included eight trials. In the subgroups of patients with predicted severe acute pancreatitis and pancreatic necrosis , results were consistently better if EN was started
within 24 h. However, these results were not statistically signifi cant. Therefore, the
current guideline is to start the enteral nutrition in the fi rst 24–48 h which is considered early by American Society of Enteral and Parenteral Nutrition standards [ 37 ].
Numerous meta-analyses have examined the use of early enteral nutrition in
severe acute pancreatitis . In a meta-analysis by Li et al. [ 38 ], early enteral nutrition
within 48 h in severe acute pancreatitis showed protection against infectious complications. There was another meta-analysis by Petrov et al. in 2008 [ 32 ] that aimed
to analyze the timing of enteral nutrition. This study showed a signifi cant risk reduction of multiple organ failure; pancreatic infectious complications; hyperglycemia;
and length of hospitalization if EN was started within the fi rst 48 h. The limiting
factor of this study was the lack of a standard defi nition for early vs. late enteral
nutrition, which varied from 24 to 72 h after admission. Taken together, the available evidence base suggests that EN can be safely initiated within the fi rst 24–48 h
after resuscitation.
Another approach used to nourish patients with acute necrotizing pancreatitis is
early volume oral feeds containing 248–330 kcal/day given to patients within the
fi rst 72 h. A retrospective study published in 2014 by Pupelis et al. [ 39 ], examined
10 years of data. In this study, there was a statistically signifi cant improvement in
CRP level, the need for surgical intervention, and ICU stay. The concept of early
oral nutrition in necrotizing pancreatitis should be further investigated in a prospective randomized study.
Future Directions
Several advances have been made in defi ning the role of nutritional support in the
treatment of severe acute necrotizing pancreatitis [ 40 ]. One of the most important
changes is the early initiation of proper enteral nutrition . The use of PN to achieve
pancreatic rest is no longer recommended. The appropriate site of tube insertion for
patients with severe acute pancreatitis and pancreatic necrosis needs to be further
elucidated.
37 Nutritional Support in Acute Necrotizing Pancreatitis
418
The use of antioxidants for patients with acute pancreatitis should be evaluated
further in a large scale study since there are studies that have shown that glutamine
or other antioxidants [ 41 ] can be benefi cial in the ICU setting.
Recommendations
In severe acute pancreatitis and pancreatic necrosis , enteral feeds are recommended
(evidence quality high: strong recommendation).
If there is normal gut function and tolerance, NG tube feeds can be attempted
(quality moderate: weak recommendation).
If there is gut dysfunction, NJ tube should be inserted (evidence quality moderate: weak recommendation).
EN should be initiated within 24–48 h after admission (evidence quality high:
strong recommendation).
A Personal View of the Data
In most of tertiary medical centers, feeding in patients with acute necrotizing pancreatitis usually starts after completion of the initial resuscitation process. The
administration of feeding stimulates the gut and preserves gut function [ 27 ].
Prolongation of intestinal dysfunction increases pancreatic infection rate and mortality [ 42 ].
There is a clear role for the use of PN in the management of severe acute pancreatitis when EN is not able to achieve nutritional goals [ 43 ] or when the route is
compromised [ 44 ] such as in the presence of ileus, enteric fi stula, pancreatic pseu-
docyst , ascites , or other severe complications. Nutrition in necrotizing pancreatitis
is an important medical decision that can infl uence the progression of the disease
and reduce complication rates. Further studies are needed to address the optimal
anatomic level used for nutrition, the use of immunonutrition, and the prophylactic
administration of probiotics.
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421© 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_38
Chapter 38
Management of Symptomatic Pancreatic
Pseudocyst
Benjamin D. Ferguson and Vivek N. Prachand
Abstract Management options for pancreatic pseudocyst are numerous and include
endoscopic and surgical approaches. Much debate exists regarding which of these
approaches is superior and when each is most appropriate. While endoscopy offers
less post-procedural pain, shorter length of stay, and fewer complications, laparoscopic surgical approaches are more suitable for pseudocysts whose locations or
other characteristics present signifi cant technical challenge or are otherwise unamenable to endoscopic drainage. Endoscopic management should be attempted when
technically feasible, and a laparoscopic approach should be employed when endoscopic drainage would be technically diffi cult or in symptom recurrence following
initial endoscopic management.
Keywords Pancreatic pseudocyst • Laparoscopy • Endoscopy • Cystgastrostomy
Introduction
Pancreatic pseudocysts are collections of pancreatic fl uid and necrotic tissue surrounded by a non-epithelial perimeter persisting for greater than 6 weeks and arising following pancreatitis or trauma. Although usually asymptomatic, pseudocysts
can cause symptoms by mass effect (abdominal or back pain , obstructive symptoms, or jaundice ), infection, or hemorrhage. Though spontaneous resolution is
typical, serious complications, such as rupture, infection, bleeding, or obstruction,
can occur. Management options can be broadly classifi ed as surgical or endoscopic .
Within the surgical domain, laparoscopy has emerged as a safe and effective method
for management of pancreatic pseudocyst s and typically is associated with less
postoperative pain, shorter length of stay, and non-inferior success rates compared
to open surgical management. Endoscopic approaches offer even less pain,
B. D. Ferguson • V. N. Prachand (*)
Department of Surgery , University of Chicago Medical Center ,
5841 S Maryland Ave , Chicago , IL 60637 , USA
e-mail:
vprachan@surgery.bsd.uchicago.edu
422
procedural invasiveness, and hospital length of stay, but may require more than one
treatment to achieve pseudocyst resolution. As a result, there is signifi cant controversy and uncertainty regarding optimal management of pancreatic pseudocyst.
Several laparoscopic surgical techniques have been described. The most common among these include pseudocystgastrostomy via anterior (intraluminal) or posterior (extraluminal) approaches, pseudocystduodenostomy, and Roux-en-Y
pseudocystjejeunostomy. Likewise, several endoscopic options have been described,
including the use of ultrasound or fl uoroscopic guidance for pseudocyst localization, plastic vs. metal stent use, single vs. multiple stent placement, and concomitant
ERCP to identify need for and facilitate pancreatic duct (PD) stent placement. For
the purpose of this review, studies involving any combination of these techniques
have been considered collectively as either laparoscopic or endoscopic management
techniques, respectively.
Search Strategy
A Medline search was performed in PubMed using the following search strings
based on PICO elements (Table 38.1 ): “pancreatic AND pseudocyst AND ( laparo-
scopic OR laparoscopy OR endoscopic OR endoscopy )”. The search was limited to
studies on human subjects written in the English language since 2000. All results
were read and reviewed, and irrelevant results were excluded from the analysis.
Single-case reports, systematic and other reviews, and editorials and commentaries
were also excluded.
Results
There is a paucity of prospective clinical trials comparing surgical and endoscopic
management of pancreatic pseudocyst s. No studies have directly compared laparoscopic management to endoscopy , and there is substantial heterogeneity in the techniques and adjuncts used in the series that are available. Furthermore, numerous
series include both pseudocysts and necrotic fl uid collections, further complicating
the interpretation of their outcomes given the reduced effi cacy of endoscopic
Table 38.1 PICO table for management of symptomatic pancreatic pseudocyst
P (Patients) I (Intervention)
C (Comparator
group) O (Outcomes measured)
Patients with
symptomatic
pancreatic pseudocyst
undergoing curative
management
Laparoscopic
operative
management
Endoscopic
management
Resolution of symptoms,
complications, recurrence, need
for additional or more invasive
management
B.D. Ferguson and V.N. Prachand